SUTRA: A novel approach to modelling post-Omicron case projections for India
SUTRA stands for Susceptible, Undetected, Tested (positive), and Removed Approach. A novel feature of our model is that it allows estimation of parameters from reported infection data, unlike most other models that estimate parameter values from other considerations. This gives the model the ability to predict the future trajectory well, as long as parameters do not change. In addition, it is possible to quantify how the model parameter values were affected by various interventions to control the pandemic, and/or the arrival of new mutants.
The SUTRA consortium consists of five members of eminent national institutions. The members are Anurag Agrawal, IGIB; Manindra Agrawal, IIT Kanpur; Pramod Garg, THSTI; Madhuri Kanitkar, MUHS and M. Vidyasagar, IIT Hyderabad.
Multi-label segmentation and detection of COVID-19 abnormalities from chest radiographs using deep learning: Study by Dr BR Ambedkar National Institute of Technology (NIT) Jalandhar
Due to COVID-19, the demand for chest radiographs (CXRs) has increased exponentially. Therefore, researchers from NIT Jalandhar present a novel and fully automatic modified attention U-net (CXAU-Net) multi-class segmentation deep model that can detect common findings of COVID-19 in CXR images. The architectural design of this model includes three novelties: first, an attention U-net model with channel and spatial attention blocks is designed that precisely localise multiple pathologies; second, dilated convolution applied improves the sensitivity of the model to foreground pixels with additional receptive fields valuation, and third a newly proposed hybrid loss function combines both area and size information for optimising model. The proposed model achieves average accuracy, DSC, and Jaccard index scores of 0.951, 0.993, 0.984, and 0.921, 0.985, 0.973 for image-based and patch-based approaches respectively for multi-class segmentation on chest X-ray 14 dataset. Also, average DSC and Jaccard index scores of 0.998, 0.989 are achieved for binary-class segmentation on the Japanese Society of Radiological Technology (JSRT) CXR dataset. These results illustrate that the proposed model outperformed the state-of-the-art segmentation methods.
Omicron chase set to change genome sequencing game plan, says scientist associated with COVID-19 diagnostics
Research centres across the country are advising genome sequencing of positive samples detected using the RT-PCR kit that uses the S gene target failure (SGTF) strategy.
The Omicron VOC-21NOV-01 (B.1.1.529) genome also contains the spike deletion at position 69-70, which is associated with S gene target failure (SGTF) in some widely used polymerase chain reaction (PCR) tests. Such PCR tests evaluate the presence of three SARS-CoV-2 genes: Spike (S), N and ORF1ab. SGTF is defined as a PCR test where the N and ORF1ab genes are detected (with Ct values <=30) but the S gene is not. SGTF patterns can be used to assess the spread of Omicron VOC-21NOV-01 (B.1.1.529).
“This will reduce the scope of our search for Omicron and make it more focused,” Nagpur based CSIR-NEERI scientist Krishna Khairnar, a key researcher in COVID-19 diagnostics in India, told TOI. There are only a handful of test kits that target S gene. “If a person tests positive using such an RT-PCR kit, we can take his or her sample for whole genomic sequencing on priority. The chances of the variant detection rise manifold. This will save a lot of time and resources as genome sequencing is costly,” he said.
IISc research has leads for COVID-19 prognosis and therapy
A recent study, led by Shashank Tripathi from Indian Institute of Science (IISc), Bengaluru reports two novel findings: a specific gene signature in nasal swabs, which can predict COVID-19 severity, and the potential offered by an FDA-approved drug (Auranofin) for COVID-19 therapy.
In the study, the researchers analysed COVID-19 data from nasopharyngeal samples and were able to identify specific genes belonging to the S100 family, which could serve as prognostic markers of severe COVID-19. This gene signature can be detected by RT-PCR in the nasal swabs, which are collected for COVID-19 diagnosis.
The researchers also identified multiple host processes that may be involved in virus replication and disease progression, and may serve as targets for host-directed therapy. Crucially, a redox regulatory protein called Thioredoxin (TXN) was found to be consistently overexpressed in COVID-19 patients. Auranofin, an FDA-approved drug that targets the enzyme thioredoxin reductase and blocks the thioredoxin pathway, was found to reduce SARS-CoV-2 replication in cell culture as well as in the hamster model. Auranofin is a safe and economical drug used for arthritis treatment. The study, therefore, suggests that it could serve as a promising COVID-19 antiviral.
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CSIR-CCMB’s dry swab RT-PCR test method gets validated
CSIR-CCMB’s novel ‘dry swab’, extraction-free direct RT-PCR testing method, which has reduced the time taken for the COVID-19 test result to be declared, got further validation with another study highlighting the ‘immense’ value of the method in the detection of any kind of variant, better sensitivity and illuminating more ‘scientific dimensions’.
In the latest issue of Journal of Biosciences, published by the Indian Academy of Sciences, the article, ‘Temporal Stability and Detection Sensitivity of Dry Swab Diagnosis’ of SARS-CoV-2, authored by scientists CG Gokulan, Uday Kiran, Santosh Kumar K. and Rakesh Mishra of CSIRCCMB, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, and Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt (Germany), discussed more advantages and scope for commercialisation as it can increase lab throughput by three-fold.
Challenges like reagent shortage, limited human resources and high transmission rate can be handled in a better manner to contain the infection and better allocation of medical resources, as it can quickly diagnose and control the spread. The study on temporal stability of two strains of SARS-CoV-2 at two different temperatures indicates that for shorter distance transportation, cold chain can be avoided and the dry swab samples with low viral load also is stable at RT for 24 hours.
In case of high sample surge, the swabs can be stored at 4°C for up to three days without compromising detection sensitivity. The method is expected to hold similar advantages in case of other emerging variants of SARS-CoV-2 as indicated by multiple sewage surveillance and sequencing studies, it said.
This suggests that while the virus variants could be different with respect to the rate of infection and eliciting immune response, they are generally stable for longer time in different conditions. Throughput of dry swab-based sample processing could be further increased by the collection of samples directly into tubes containing the ‘TE-P buffer’. Since no transportation is required, it would increase the turnover time drastically when thousands of samples are being tested.
Data indicates that dry swab method correlates well with the conventional method. Lesser CT values of dry swab samples in comparison to that of the VTM-RNA samples suggest better sensitivity of the method within 48 hours of time. Dry swab samples are also found to be stable at RT for 24 hours and the detection of SARS-CoV-2 RNA by RT-PCR does not show variance from VTM-RNA. This extraction-free, direct RT-PCR method holds phenomenal standing in the present life-threatening circumstances due to COVID-19.
Website link: https://pubmed.ncbi.nlm.nih.gov/34728592/
IIT Palakkad analyses COVID-19 impact on children suffering from Kawasaki disease
During the early days of the COVID-19 pandemic, medical doctors in Europe and the US found a small section of young patients either recovered from COVID-19 or previously exposed to SARS-CoV-2 developing a novel multi-systemic disease condition, which has a close resemblance to an earlier-known illness called Kawasaki disease.
Called Multisystem Inflammatory Syndrome in Children (MIS-C) in the US and Paediatric Inflammatory Multisystemic syndrome (PIMS) in Europe, the new condition had several overlapping symptoms and manifestations similar to that of Kawasaki disease, prompting a section of experts to speculate that both belonged to the same disease spectrum.
IIT Palakkad scientists provide critical analyses on how COVID-19-triggered inflammatory disease in children is different from Kawasaki disease. A team of international researchers led by an Indian scientist, who analysed reports emerging from different labs around the world, has concluded that they are distinctly different diseases even though they share many symptoms and elicit a somewhat similar immune response. They also found that Kawasaki disease and MIS-C have varying degrees of hyper inflammation and misdirected immune responses.
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IIT Kanpur working to develop a novel therapeutics for COVID-19
IIT Kanpur’s Dr Arun Shukla and his team, Department of Biological Sciences and Bioengineering, have described the working mechanism of a new class of receptors that were earlier believed to be ‘silent’ or ‘non-functional’. This discovery opens up the possibility of targeting these receptors for novel therapeutics development in multiple inflammatory disorders like COVID-19 as well as rheumatoid arthritis and sepsis.
Shukla and his team have shown that the two specific GPCRs they studied, D6R and C5aR2, both of which were classified as non-signalling GPCRs, could transmit a signal through Arrestins, but not G Proteins. The current discovery highlights a non-classical signalling mechanism induced by two receptors that are structurally similar to GPCRs. Almost half the current drugs in the market, including drugs for hypertension, asthma, allergy, acidity, cancer and more, target GPCRs. The drugs work by blocking the GPCR region that can stimulate the G protein – then, the cell will fail to respond to the signal. This is medically useful, especially if the signal triggers the cells to produce, say, an allergic reaction.
Scientists are currently trying to block the interaction of the C5a peptide with C5aR1 as a potential therapy in certain COVID-19 cases. The understanding from the present study could now allow the development of drugs targeting C5aR2, in addition to C5aR1.
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IISc developed online self-assessment tool for workplaces: COVID-19 readiness indicator tool
With COVID-19-related restrictions easing and many workplaces slowly resuming work, an online self-assessment tool known as the COVID-19 Workplace Readiness Indicator has been developed by a team of researchers led by Rajesh Sundaresan at the Department of Electrical Communication Engineering, in collaboration with the Karnataka State Disaster Management Authority (KSDMA). It was designed as part of research efforts at the new Centre for Networked Intelligence established at IISc with CSR support from Cisco.
The tool takes into account broad epidemic factors and social objectives. It suggests a simple readiness threshold that organisations need to meet or exceed to operate effectively while managing their pandemic response. An organisation can enter information about their workplace and current level of operation into the website, then calculate their readiness level using 10 specific indices, each with a maximum score of 100, and provide a consolidated report. It also provides targeted suggestions if particular weaknesses are identified.
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Website link: https://covid.readiness.in/
Creating scientific resources for outreach initiatives by CESSI at IISER Kolkata on COVID-19
The Center of Excellence in Space Sciences India (CESSI), IISER Kolkata have utilised their in-house modelling and data analytics capabilities to create resources intended for spreading scientific awareness about the pandemic among the general public and guiding future policies related to the same. The resources available here are based on the CESSI-nCoV-SEIRD model, which has been optimised for the Indian context at IISER Kolkata, data analysis of India specific and some global data on the progress of the pandemic, and informational graphics and social media messages created by the Indian Scientists’ Response to COVID-19 (ISRC) group – to which IISER Kolkata scientists have contributed.
Further, details on the epidemiology model developed at CESSI can be found in the ‘Model’ section. India-specific information on the disease progression and critical parameters characterising the progression of the pandemic can be found in the ‘Data Analytics’ section. Socio-scientific awareness materials can be found in the ‘Public Outreach’ section. Researchers from CESSI have also analysed the COVID-19 progression for different Indian states and cities, which can be found out by selecting the name of the state or the city in the dashboard.
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Website link: http://www.cessi.in/coronavirus/
PDE-based modelling of COVID-19 infections developed by IISc
Researchers from Indian Institute of Sciences (IISc), Bengaluru has developed a model, which is based on a high-dimensional population balance equation. The model predicts the distribution of infected population across the region, the age of the infected people, the day since infection, and the severity of infection, over a period of time. Moreover, the developed model also incorporates the immunity, pre-medical history, effective treatment, point-to-point movement of infected population (e.g., by air, train, etc), interactivity (community spread), hygiene and the social distancing of the population
AMCHSS developed an interactive dashboard to visualise the COVID-19 situation in India
Achutha Menon Centre for Health Science Studies (AMCHSS), a centre of excellence for public health, developed an interactive dashboard to visualise the COVID-19 situation in India. The dashboard uses data science and epidemiological methods to monitor and track the spread of COVID-19. It offers insights into the transmission dynamics and progression of the epidemic to the public health programme managers, scientific community and general public. The dashboard is updated on a weekly basis. This dashboard gives the information of total confirmed cases, total active cases, total recovered cases, total deceased cases and percentage of active COVID-19 cases in India in the last week.
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Website link: https://amchss-sctimst.shinyapps.io/covid_dashboard/
IIT Bombay, in association with city-based Kasturba Hospital, develops technology that can measure the severity of COVID-19
India’s COVID-19 cases saw a massive surge in March and April 2021. The second wave of the COVID-19 pandemic put a lot of pressure on the medical infrastructure. Appropriate medical facilities were at times not available to those who needed them the most — the ones who had severe symptoms. There was no way to predict how severe the symptoms of an infected person could become. The golden test to check for COVID-19, the RT-PCR test can only tell whether a person is infected or not. Unfortunately, the test cannot determine the severity of the infection.
Researchers from the Indian Institute for Technology Bombay (IIT Bombay) and Kasturba Hospital for Infectious Diseases, Mumbai, led by Prof Sanjeeva Srivastava of IIT Bombay, have found that levels of specific proteins in the nasopharyngeal samples of a person can differentiate between low and high severity of infection. This information would help hospitals distribute healthcare resources on time and ensure that those who require critical care could be identified with relative ease. The study was funded by the Council of Scientific & Industrial Research (CSIR) and IIT Bombay.
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All India Institute of Ayurveda to conduct clinical trials of Ashwagandha for COVID-19
Ashwagandha, commonly known as ‘Indian winter cherry’, is a traditional Indian herb that boosts energy, reduces stress, and strengthens the immune system. The All India Institute of Ayurveda (AIIA), in collaboration with UK’s London School of Hygiene & Tropical Medicine (LSHTM), is conducting a study on Ashwagandha to promote recovery from COVID-19. AIIA and LSHTM signed a Memorandum of Understanding to conduct clinical trials on Ashwagandha on 2,000 people in three UK cities – Leicester, Birmingham, and London (Southall and Wembley).
It has also been indicated for treating non-restorative sleep, a hallmark of chronic fatigue, for which the trials are currently on. Combined with substantial literature on its pharmacological and immunomodulatory effects in vitro and in animals, the study suggests Ashwagandha as a potential therapeutic candidate for alleviating the long-term symptoms of COVID-19.
Dr Tanuja Nesari, Director, AIIA said that the study is approved by the Medicines and Healthcare Products Regulatory Agency (MHRA) and certified by WHO-GMP
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India to enhance surveillance of SARS-CoV-2 through viral genome sequencing to monitor future trajectory of COVID-19
Facilitated by the Office of the Principal Scientific Adviser to the Government of India, Rockefeller Foundation has agreed to provide funding to an Indian consortium consisting of research institutions from Hyderabad, Pune, Bengaluru, and Delhi. Led by Council of Scientific and Industrial Research -Centre for Cellular and Molecular Biology (CSIR-CCMB) in Hyderabad, the consortium will bring together key partners to upscale genome surveillance across India by ramping up genome sequencing efforts, bioinformatics, and data sharing. It will complement the efforts of the Indian SARS-COV-2 Genome Sequencing Consortium (INSACOG).
The enhanced genome surveillance will help India track the emergence and transmission of new SARS-CoV-2 variants and correlate them with epidemiological dynamics and clinical outcomes of patients. This will, in turn, help health policymakers to draw inferences from clinical outcomes and implement appropriate public health and medical countermeasures. The information generated through genome surveillance will feed into research on the improvement of vaccines, diagnostics, and developing therapeutics.
With the phenomenon of vaccine breakthrough (when vaccinated people get infected), now recognised as a key aspect of COVID-19 research efforts, the research consortium will also use the Rockefeller funding to better understand the genomic characteristics of the virus that allow it to escape vaccine-mediated immunity.
The surveillance system created through this initiative will also be useful in the timely tracking of future infectious disease outbreaks and to better understand and mitigate anti-microbial infections in the country.
Along with CSIR-CCMB Hyderabad, the research consortium consists of other prominent research institutions such as Pune Knowledge Cluster, National Centre of Biological Sciences (NCBS), and DBT-Institute for Stem Cell Science and Regenerative Medicine (DBT-InStem) in Bengaluru, and CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) in Delhi.
IISc develops blood-based biomarker for differential diagnosis and recovery monitoring of acute viral and bacterial infections
A recent study from IISc, Bengaluru has identified a set of molecular biomarkers that can be used in the differential diagnosis of acute bacterial and viral infections. The biomarkers are messenger RNA (mRNA) molecules found in the blood. Differences in their levels can, with high probability, predict if an infection is viral or bacterial.
A quick method to detect acute viral and bacterial infections and distinguish between them can be immensely useful in the clinic, as accurate diagnosis will win half the battle and guide the clinician towards the optimal treatment path. It will also prevent the rise of such antimicrobial resistance.
The authors suggest that the test could be useful for differentiating COVID-19 infection from bacterial infections as well. In the study, they looked at various viral infections for which transcriptomic data is publicly available. This allowed them to develop a generic VB10 test score for viral infections. As soon as transcriptomic data became available for COVID-19, the team tested their approach and found that the test scores could differentiate between SARS-CoV-2 infection and common bacterial respiratory infections. This work was done in collaboration with clinicians at MS Ramaiah Medical College and researchers Amit Singh, Dipshikha Chakravortty and KN Balaji at IISc.
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IISc’s research is geared towards making drone flight more efficient for healthcare, transportation and other services
Unmanned Aerial Vehicles (UAVs), popularly known as drones, are small aircrafts that fly without a pilot. Drones can weigh anywhere from a few grams to over 100 kilograms, depending on their use. They either have a ground-based controller or are completely autonomous, with a built-in controller in the form of a computer program that guides them.
UAVs have a wide range of applications including surveillance, cargo transport, warfare, agriculture, journalism and recreation, to name a few. These vehicles have also been of great help during the COVID-19 pandemic, in remote surveillance and disinfection of areas
Ashwin Ratnoo’s team develops algorithms that plan and control the trajectories of UAVs, particularly in complex and urban settings. It is not easy to organise timely delivery of medicines or organs for transplantation in a crowded city. A lot of manpower is involved, and elaborate traffic management is needed if they are transported by road. This is an easy job for a drone, but flying one over a populous urban space comes with many safety concerns, explains Ashwini. That is why drones are still not being used to their full capacity and potential.
To address this issue, his lab is working on developing ‘Drone Skyways’ in collaboration with the Robert Bosch Centre for Cyber Physical Systems (RBCCPS) and ARTPARK at IISc. The team developed ‘CORRIDRONE’, a novel drone skyway framework with an efficient design that includes geo-fencing, a virtual fence along the corridor. CORRIDRONE allows for safe pointto-point movement of multiple drones without collision and can be set up in any given airspace.
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Clinical characteristics, outcomes, and mortality in pregnant women with COVID-19 in Maharashtra, India: Study by ICMR
An ICMR study has found that coronavirus may infect a higher proportion of pregnant women leading to moderate-to-severe diseases. The most common complications were pre-term delivery and hypertensive disorders in pregnancy. The analysis was based on the data from the PregCovid registry, a study of pregnant women and women in the post-partum period with a confirmed diagnosis of COVID-19.
The PregCovid registry prospectively collects information in near-real time on pregnant and post-partum women with a laboratory-confirmed diagnosis of SARS-CoV-2 from 19 medical colleges across Maharashtra, India. The data of 4203 pregnant women were collected during the first wave of the COVID-19 pandemic (March 2020-January 2021) and then it was analysed. Out of 4203 data collected, there were 3213 live births, 77 miscarriages and 834 undelivered pregnancies. The most common complication was preterm delivery (528, 16.3%) and hypertensive disorders in pregnancy (328, 10.1%). A total of 158 (3.8%) pregnant and post-partum women required intensive care, of which 152 (96%) were due to COVID-19 related complications.
The overall case fatality rate (CFR) in pregnant and post-partum women with COVID-19 was 0.8 per cent (34/4203). Higher CFR was observed in Pune (9/853, 1.1%), Marathwada (4/351, 1.1%) regions as compared to Vidarbha (9/1155, 0.8%), Mumbai Metropolitan (11/1684, 0.7%), and Khandesh (1/160, 0.6%) regions. Comorbidities of anaemia, tuberculosis and diabetes mellitus were associated with maternal deaths.
NCBS-TIFR studies strategies to target SARS-CoV-2 entry and infection using dual mechanisms of inhibition by acidification inhibitors
Many viruses utilise host endo-lysosomal network for infection, so tracing the endocytic itinerary of SARS-CoV-2 can provide insights into viral trafficking and aid in designing new therapeutic strategies. Here, researchers from InStem demonstrate that the receptor binding domain (RBD) of SARS-CoV-2 spike protein is internalised via the pH-dependent CLIC/ GEEC (CG) endocytic pathway in human gastric-adenocarcinoma (AGS) cells expressing undetectable levels of ACE2. Ectopic expression of ACE2 (AGS-ACE2) results in RBD traffic via both CG and clathrin-mediated endocytosis. Endosomal acidification inhibitors like BafilomycinA1 and NH4Cl, which inhibit the CG pathway, reduce the uptake of RBD and impede Spike-pseudoviral infection in both AGS and AGS-ACE2 cells. The inhibition by BafilomycinA1 was found to be distinct from Chloroquine, which neither affects RBD uptake nor alters endosomal pH yet attenuates Spike-pseudovirus entry. By screening a subset of FDAapproved inhibitors for functionality similar to BafilomycinA1, they identified Niclosamide as a SARS-CoV-2 entry inhibitor. Further validation using a clinical isolate of SARS-CoV-2 in AGSACE2 and Vero cells confirmed its antiviral effect. Researchers propose that Niclosamide, and other drugs which neutralise endosomal pH as well as inhibit the endocytic uptake, could provide broader applicability in subverting infection of viruses entering host cells via a pHdependent endocytic pathway.
IIT Bombay studies severity of COVID-19 infection
Researchers from the Indian Institute for Technology Bombay (IIT Bombay) and Kasturba Hospital for Infectious Diseases, Mumbai, led by Prof Sanjeeva Srivastava of IIT Bombay, have found that levels of specific proteins in the nasopharyngeal samples of a person can differentiate between low and high severity of infection. This information will help hospitals distribute health care resources on time and ensure that those who require critical care can be identified with relative ease.
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Homemade face masks – effectiveness varies depending on how they are made, says IISc study
Since the spread of virus causing COVID-19 continues, experts recommend wearing homemade facemasks when surgical or N95 masks are not available to prevent the spread of the pandemic. While such makeshift masks are more economical and accessible in low-capita countries, the effectiveness of cloth masks has not been studied in depth.
Researchers at Indian Institute of Science (IISc) have carried out a detailed study on the fate of a large-sized surrogate cough droplet impinging at different velocities (corresponding to mild to severe coughs) on various locally procured cloth fabric (stole, handkerchief, cotton towel, and surgical masks), specifically those which are convenient for people to use every day.
A single quantity has been formed by combining the individual effects of pore size and porosity, giving a better insight into the correlation between liquid penetration and fabric properties. Based on their findings, the researchers recommend using a cotton towel (with at least three layers) as a face covering if the person cannot use an N95 or a surgical mask. Masks with three or more layers are ideally recommended since they can suppress aerosolisation significantly. The team also analysed the effect of washing on mask effectiveness. Results show, up to 70 wash cycles, a negligible influence of washing on mask efficacy.
This study was carried out by Bal Krishan, Dipendra Gupta, Gautham Vadlamudi and Shubham Sharma under the guidance of Prof Saptarshi Basu and Prof Dipshikha Chakravortty.
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Website link: https://aip.scitation.org/doi/10.1063/5.0061007
Modelling the impact of sensor performance on epidemic management: A study by IISc
The mathematical modelling of epidemic dynamics is a rich field with a large diversity of available models, accounting for various aspects of the problem. The study proposes to create a discrete, stochastic agent-based network model where each agent has a set of associated contacts, and a mobility pattern matching observed statistical distributions. The number of infected persons is estimated based on a testing technology with specified error rates. This simulation set-up will allow us to quantitatively evaluate the impact of various testing and sampling strategies on broader epidemic management.
The study attempts to add an essential additional layer into conventional epidemic models, namely, and disease testing technologies.
The model enables one to find an optimum allocation of tests to manage the epidemic spread. The simulation framework proposed will address several critical issues necessary for effective epidemic management.
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Network-based novel target identification and drug repositioning for novel coronavirus by IIIT Hyderabad and CSIR-IMTECH
A team of researchers from IIIT Hyderabad identifies relevant targets (both viral and host) by expansive analysis of the viral-host interactome at multiple levels and screening for possible drug molecules that effectively inhibit these targets using traditional molecular design methods and modern artificial intelligence/machine learning algorithms. The identified drug molecules will then be tested at CSIR-IMTECH using Vero E6 plaque assay for further development.
They have also developed a method based on reinforcement learning and docking methods for de novo molecular generation. Both these methods have been applied to identify novel molecules that strongly bind to the main proteinase of SARS-CoV-2.
The project has addressed three fundamental aspects related to COVID-19 – drug repurposing based on the analysis of host SARS-CoV-2 metabolic interactome; machine learning-based risk stratification and mortality prediction of COVID-19 positive patients; and molecular design for SARS-CoV-2 main proteinase using machine learning and physics-based methods. This would tremendously help reduce the computational effort in drug discovery and areas that require such high-throughput experiments.
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AIIMS Delhi studies single-dose oral Ivermectin as a potential treatment for COVID-19 patients
Ivermectin has been suggested as a treatment for COVID-19. This randomised control trial was conducted to test the efficacy of Ivermectin in the treatment of mild and moderate COVID-19, at All India Institute of Medical Sciences (AIIMS) Delhi.
The study aimed to evaluate the efficacy of single-dose Ivermectin in reducing viral load in COVID-19 patients. Also, they considered the effectiveness of Ivermectin in time for clinical improvement, the percentage of patients progressing to severe disease, and the frequency of adverse events in both arms. The study hypothesises that single-dose Ivermectin will significantly reduce viral load (as estimated by RTPCR) and reduce the primary reproductive number (R0) for COVID-19.
They performed an open-label randomised controlled trial of single-dose Ivermectin (various doses, i.e., 12 mg, 24 mg, 48 mg, 96 mg and 120 mg) in admitted COVID-19 patients with nonsevere illness and without contraindications to Ivermectin administration.
Significance of outcome of the research: Reduction in viral load, if achieved, can lead to early discharge of patients from the hospital. Also, as the persistent viral load correlates to progression to severe disease and complications in the second week of illness, Ivermectin can lead to reduced incidence of progression to severe disease and respiratory failure. Another important aspect is that by reducing the duration for which a patient remains infected, Ivermectin can reduce the primary reproductive number (R0) for COVID-19. If found effective, it can be evaluated and considered for single-dose administration. This can become one important strategy in flattening the curve of this pandemic.
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RGCB develops anosmia checker, a rapid and low-cost alternative tool for mass screening of COVID-19
COVID-19 is an ongoing pandemic, with 80 per cent of patients showing only mild symptoms. Of this, 20 per cent are asymptomatic. These asymptomatic patients do not display any signs but are capable of shedding the virus and acting as carriers of COVID-19. Therefore, it is essential to identify these asymptomatic carriers and quarantine them to stop the spread of COVID-19. The only way to determine the asymptomatic carriers is to conduct mass screening, but current diagnostic kits have limitations. Considering the inability of different diagnostic platforms to independently screen and identify the asymptomatic carriers, researchers from Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, are working on multiple platforms together to identify the asymptomatic carriers among the masses and confirming infection using confirmatory media.
It is known that SARS-CoV-2 first infects the nasopharyngeal region leading to loss of smell. Hence, they hypothesised that this would be the first indicator of COVID-19 infection. Therefore, they are developing a low-cost initial screening tool using the initial loss of smell as an indicator that needs to be carried out and other confirmatory protocols.
The study proved to predict COVID-19 infection by calculating a loss of smell score with 100 per cent specificity
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ILBS identifies COVID-19 associated extracellular vesicles as a prognostic tool and an alternative of SARS-CoV-2 infection and transmission
The COVID-19 illness has a broad range of clinical manifestations, from asymptomatic or mild infection to a severe respiratory disease progressing to respiratory and multi-organ failure.
Extracellular vesicles (EVs), including microvesicles (MVs), or exosomes have been shown to serve as vehicles for intercellular communication and transfer of genetic material in several viral infections. Therefore, it was reasonable to hypothesise that EVs may serve as reservoirs of SARS–CoV-2, transmit COVID-19 disease to naïve cells and the EV associated SARS-CoV-2 RNA might also contribute to reactivation after the viral clearance.
This study, conducted at Institute of Liver and Biliary Sciences, found that all confirmed COVID-19 patients, positive in nasal swab also had extracellular vesicles (EV) associated viral RNA. In the same patients, it was undetected in the plasma but positive in EV associated SARS-CoV-2 RNA in one per cent of patients. Interestingly, the EV associated was of endothelial cells of origin as detected using flow cytometry.
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Modelling, analysis and prediction for SARS-CoV-2 infections by IISER Thiruvananthapuram
Prediction of the dynamics of new SARS-CoV-2 infections during the current COVID-19 pandemic is critical for public health planning of efficient health care allocation and monitoring the effects of policy interventions.
The susceptible-infected-recovered (SIR) model is the most classic and popular epidemic model to simulate the spreading of infectious diseases. By this model, one tries to understand how different situations may affect the outcome of the epidemic and to answer questions, like what is the most efficient technique for administering a limited number of vaccines in a given population.
With the basic SIR model, the importance of primary reproductive number (R0) has been studied by the team led by Dr Utpal Manna, Indian Institute of Science Education and Research (IISER) Thiruvananthapuram. The SIR model tries to compute the theoretical number of people infected with a contagious illness in a closed population over time, and the total number of infected persons or the duration of an epidemic. As COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emergent virus, there is much to be understood about its transmission.
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IISc studies droplet generation from eyes for pathogen transmission
A common eye test could expel tear droplets up to a meter away from the patient, potentially spreading virus that causes COVID-19 and other pathogens. In physics of fluids, scientists from IISc and the Narayana Nethralaya Foundation explain how tears ejected from the eye during a glaucoma test can theoretically transmit disease.
The researchers modelled the eye’s response and took high speed images of eyes undergoing the procedure. They were specifically looking at the liquid in the eye and how it responded. As the eye was hit with the air puff, the film of tears on the surface expanded into a sheet that spilled out over the eyelids. The cornea also deflected away from the incoming air. The waves move within the eye and tear liquid eventually becomes unstable, and the tears break up into droplets. The team tracked the speed of those droplets as they left the eye and predicted they could travel up to a meter away from the patient. The distance depends on the air flow within the room.
This work can help eye care practitioners to develop and follow health and safety protocols, like improved room ventilation and cleaning nearby instruments and surfaces, that may not have been considered necessary in the past.
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Website link: https://aip.scitation.org/doi/10.1063/5.0061956
IIT Palakkad develops an automated lung ultrasound workflow for diagnostic assistance in COVID-19
In the case of SARS-CoV-2 infection, it has been reported that lung abnormalities may develop before clinical manifestations and nucleic acid detection. Hence, early chest computerised tomography (CT) has been recommended for screening suspected patients. However, the high contagiousness of SARS-CoV-2 and the risk of transporting unstable patients with hypoxemia and hemodynamic failure make chest CT a limited option for a patient with suspected or established COVID-19. It has been reported that lung ultrasonography (LUS) gives similar results to chest CT and is superior to standard chest radiography for evaluating pneumonia and acute respiratory distress syndrome (ARDS). LUS has the added advantage of ease of use at the point of care, repeatability, absence of radiation exposure, and low cost.
An IIT team led by Professor Mahesh R Panicker has developed a lightweight algorithm based on ‘you look only once version 5’ (YOLO5) and single-shot detection (SSD) that has the capability of providing the quality of images based on the identification of various LUS landmarks, prediction of severity of lung infection and the possibility of active learning, based on the feedback from clinicians.
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IIT, BHU to use drug repurposing strategy to target SARS-CoV-2 main protease for treating COVID-19
The research group of Prof. Vikash Kumar Dubey from IIT, BHU, is working on developing new drug candidates against SARS-CoV-2 by exploring DrugBank (DrugBank is a database of FDA approved drug compounds) database compounds as an inhibitor of SARS-CoV-2 main protease, a key enzyme required for SARS-CoV-2 assembly and multiplication.
Taking advantage of available crystal structure of the SARS-CoV-2 main protease, a structurebased inhibitor design will be made by the researchers from the available FDA approved drugs compounds in the DrugBank database.
Subsequently, experimental validation of the designed inhibitor(s) on recombinant SARS-CoV-2 Mpro Protein will be carried out. Various inhibitor parameters will be calculated to establish the effectiveness of the inhibition of the SARS-CoV-2 Mpro enzyme function. As the enzyme SARS-CoV-2 Mpro, is key for processing and polyprotein for virus assembly, the inhibition of this key protein can have an antiviral effect. As most of DrugBank database compounds are characterised in terms of pharmacokinetics and toxicity, the identified molecule could be brought to the market rapidly.
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National Research Centre on Equines (NRCE) to develop hostdirected antivirals for COVID-19 patients
The Department of Science & Technology (DST) has approved support for a study by the ICAR-NRCE from Hisar in Haryana, which will screen their library of 89 small molecule chemical inhibitors for antivirals against coronaviruses.
Classically, antiviral drugs are developed by directly targeting viral proteins. However, this approach has been unsuccessful due to rapid generation of drug resistant escape variants. Being intracellular parasites, viruses are highly dependent on cellular factors. Therefore, the cellular factors that are dispensable for the host but are essential for virus replication can be targeted for antiviral drug development. They collected 89 small molecule chemical inhibitors that are known to target cellular kinases, phosphatases and epigenetic modifiers. This library of chemicals has been screened to identify potential candidates with antiviral activity against the family members of Poxviridae, Paramyxoviridae, Orthomyxoviridae, Herpesviridae and Arenaviridae.
This study aims to screen the entire library of small molecule chemical inhibitors for their antiviral action against coronavirus-infectious bronchitis virus (IBV). The selected candidates with antiviral activity against IBV will be subjected to study their molecular mechanism of action, besides examining generation of potential drug resistant virus variants. Targeting host factors could have a significant impact on multiple virus genotypes and provide broad spectrum inhibition against different families of viruses, which might use the same cellular pathway(s) for replication. Therefore, the drug candidates active against IBV may be repurposed for antiviral drug development against COVID-19.
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Stem cell derived exosome therapy for clinical management of lung damage in critically-ill corona viral pneumonia patients
A recent study by Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), hypothesises to explore the Mesenchymal Stem Cell (MSC)-derived extracellular vesicles, otherwise called exosomes, as a potential regenerative regime for lung regeneration in ARDS mice models.
They hypothesise that the immuno-modulatory and the reparative properties of MSC-derived exosomal fractions will aid in controlling the cytokine storm and lung tissue regeneration in critically ill COVID-19 patients. In this project, they first isolate MSCs from Wharton’s jelly of umbilical cord (WJ-MSCs) from healthy donors after taking informed consent. Subsequently, sub-confluent WJ-MSCs in culture will be grown in serum-free medium, the used medium will be collected and subjected to ultra-centrifugation to obtain exosomal fraction. Surface marker (CD63, CD81 and TSG101), total particle number, size and total protein content analysis of resultant exosome fraction will be characterised as per reported protocols. To assess the regenerative potential of this exosomal fraction, they will develop an acute lung damage model in SD rats (n=6/group) and treat the animals with exosome based inhalation formulation. One group provided with WJ-MSCs and another group without any treatment would be considered for comparison. The extent of lung vascular remodeling, alveolarisation and pulmonary hypertension will be assessed. Further, one of the challenges in MSC-based therapies is the limited number of availability at source and requirement of large number of cells for clinical application. In this project, they will also work on development of ex-vivo expansion system using novel cell carriers. Overall, the project aims to offer WJ-MSC-exosomal-based therapy for lung regeneration in critically-ill patients suffering from pneumonia caused by SARS-CoV-2 in particular and any other lung damage with similar pathophysiology.
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Artificial intelligence in COVID-19 drug repurposing
Drug repurposing or repositioning is a technique whereby existing drugs are used to treat emerging and challenging diseases, including COVID-19. Drug repurposing has become a promising approach because of the opportunity for reduced development timelines and overall costs. In the big data era, artificial intelligence (AI) and network medicine offer cutting-edge application of information science to defining disease, medicine, therapeutics, and identifying targets with the least error.
They want to develop a model harnessing AI and ML approaches that can be able to select and prioritise drugs according to descriptor properties in a lesser time. The drug target selection involves two way strategies: one to identify targets in virus, and other to identify proteins or enzymes in human that are required for virus attachment and entry inside the host cell. Virtual screening and docking approaches will be preferred to find correct orientation of ligand at the active site. Nowadays molecular dynamics simulations allow the observation of unsupervised ligand−target binding, assessing how these approaches help in optimising target affinity and drug residence time toward improved drug efficacy. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding. So, they want to monitor and analyse the dynamics of drug-receptor interaction in real time using molecular dynamics simulations. Their proposed machine learning-based models can be able to promote data-driven decision making and has the potential to speed up the drug discovery process and reduce failure rates in drug discovery and development. The identified potential repurposed drugs from this project will aid in facilitating the hunt of anti-COVID-19 drug discovery. Dr Manoj Kumar Yadav from SRM University, Sonepat, Haryana has successfully identified 75 compounds with an accuracy range of 70-100 per cent as active compounds against SARSCoV-2 spike protein.
All the screened compounds will be further investigated using molecular docking protocols and MD simulation in the next part of their work.
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In-silico analysis of COVID-19 genome sequences of Indian origin for identification of genetic variability and molecular targets
A researcher group from National Institute of Technical Teachers’ Training and Research, Kolkata was working on ‘in-silico analysis of 10,000 genomic sequences of COVID-19 around the world, including India to identify genetic variability and potential molecular targets in virus and humans’. The primary objectives of this project were to: (a) identify the genetic variability in SARS-CoV-2 genomes around the globe including India; (b) identify the number of virus strains using single nucleotide polymorphism (SNP) data; (c) identify the putative epitopes as candidates of synthetic vaccine, based on genomic conserved regions that is highly immunogenic and antigenic; and (d) identify the potential target proteins of the virus and human host, based on protein-protein interactions as well as by integrating the knowledge of genetic variability. In addition to these, other objectives like prediction of coronavirus from other pathogenic viruses using machine learning; and identification of virus miRNAs that are also involved in regulating human mRNA or vice-versa were also considered to explore the challenges of COVID-19 from multiple directions to give best possible answer to combat the spread of SARS-CoV-2.
This project addresses such needs by developing a pipeline for systemic analysis of virus genomes. Multiple sequence alignment of 10664 SARS-CoV-2 sequences/genomes from 73 countries including India was performed. Thereafter, a consensus sequence was built to analyse each genome to identify mutations points as substitutions, deletions, insertions and SNPs, thereby resulting in 7209, 11700, 119 and 53 such points, respectively in coding regions. Subsequently, hierarchical clustering was used on SNP data to identify virus strains. As a result, five major clusters or virus strains were identified. Furthermore, using entropy values corresponding to the genomic coordinates of the aligned sequences, conserved regions were also identified. After filtration of these conserved regions, on the basis of length, one conserved region was identified as target in the NSP6 gene and its primers and probes were identified to detect SARS-CoV-2. These refined conserved regions were then considered to identify highly immunogenic and antigenic T-cell and B-cell epitopes.
As a result of this project, 30 MHC-I and 24 MHC-II restricted T-cell epitopes with 14 and 13 unique HLA alleles and 21 B-cell epitopes were identified for the 17 filtered conserved regions
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A network optimisation-based prediction model for COVID-19 outbreak developed by IIT Kharagpur
Dr Goutam Sen from IIT-Kharagpur is working on network optimisation-based prediction model for COVID-19 outbreak. The project is supported by the Science and Engineering Research Board (SERB), a statutory body under DST, Government of India, under the MATRICS scheme for studying mathematical modelling and computational aspects to tackle the COVID-19 pandemic.
Modelling of COVID-19 spread and other similar infectious diseases is a significantly challenging task due to the inherently stochastic contagion process. The Arogya Setu app developed by MeITY, Government of India, is a significant step forward to create a mechanism of location tracking of registered mobile numbers.
The epidemiological problem can be modelled as a constrained Steiner tree problem, which is NP-hard. So, an efficient heuristic algorithm is proposed to design to solve the underlying optimisation model and test its performance using a contagion simulation episode. A SIRbased agent simulation model has been developed to create benchmark dataset. The model’s inputs are carefully constructed from the features of COVID-19. For generating test dataset, a contagion episode is simulated following a stochastic contagion process. In this simulation, the transmission probabilities are estimated from the link level data (i.e. date and duration of contact, and some other demographic factors). The performance of the optimisation model and heuristic algorithm will be tested using these simulated datasets. Further, an optimisation model is developed to identify the most influential contacts in a network so that they can be targeted for testing and isolation. The validation of the model is in process.
In the network analysis and agent-based simulation, it has been observed that there are a handful number of people who are responsible for the explosive growth of the number of cases. These people are known as super spreaders and can be easily detected as hubs in the contact network. So, under limited resources, the model helps to target very specific people to testing and isolation, thus containing the spread of the disease.
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DECOVID: Data-assimilation and error correction of viral infectious disease models – study by IISc, Bengaluru
A team of researchers from Indian Institute of Science (IISc), Bengaluru, is working on a project that will study the new data assimilation and error correction theory for infectious disease models, numerical schemes and scalable computational systems to implement Bayesian data assimilation.
Several dynamical models are available for forecasting the spread of infectious diseases such as SIR, SEIR, SIS. These are differential equation based models that seek to model a complex phenomenon with several unknowns. The goal of the present project is to develop numerical schemes and algorithms for a Bayesian data assimilation methodology to rigorously correct forecast errors of differential equation-based viral infectious disease dynamical models, and to improve their prediction skill. The technology will be used to correct model errors due to uncertainty in any forward infectious disease model that is used in practice.
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A mathematical framework for estimating risk of airborne transmission of coronavirus
COVID-19 has posed severe challenges to public health responses across countries. Mitigation and containment tactics have largely relied on the initially held belief that COVID-19 is a respiratory infectious disease that relies on droplet transmission not airborne transmission
The current study will model the aerosolised transmission of pathogens via turbulent expiratory events – coughing, sneezing and even exhaling. Many body hydrodynamics of a droplet cluster, mimicking a cough/sneeze will be simulated, to obtain a better understanding of dropletairborne transmission of diseases. The role of polydispersity, hydrodynamic interactions, background turbulence, preferential concentration and droplet wake dynamics on the ‘cough cloud’’ will be studied.
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The epidemiology and clinical information about COVID-19: A study by IIT Bombay
The research group of Dr. Mandar M Inamdar from Indian Institute of Technology (IIT) Bombay is working on the development of a general, cell-based model of 2D viral spread in a tissue in which cells are mechano-chemical entities that can deform, move, divide, and die. An additional layer of SARS-CoV-2 related kinetics will be provided for each cell that includes virus load per cell and the intensity of immune response. By modulating cell division rate, cellular motility diffusion rate of free virus, rate of cell-cell virus transfer, cell-lysis rate, and initial infection seeding, a landscape of infection patterns will be generated to understand the intensity of viral infection. Not surprisingly, the tissue-spread model is the in-host analog of infection spread in a population, where each cell within the tissue is the counterpart of an individual agent in an epidemiological model.
The long-term goal of this project is to extend the knowledge from this project to gain multi-level insights into the COVID-19 pandemic by studying the connection between in-host viral spread (immediate goal), population-level epidemiology, and the underlying molecular evolution.
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The spatiotemporal estimation of the risk and the international transmission of COVID-19: A domestic and global perspective
The study proposed to investigate three key aspects. First, spatial propagation is a key aspect behind the spread of COVID-19. Understanding the propagation mechanism is of paramount importance for preventive and corrective actions to be effective. It is proposed to combine the two critical components, namely temporal and spatial, into a single modelling framework of hierarchical models. While random effects models for such scenarios exist in literature, the study aims to extend them in two directions to facilitate the following: (a) allow to model nested nature of the data (such as districts within states); and (b) enable incorporation of covariates (for instance, climatic variables, mobility, economic factors, population size/density, biological variables). Second, the natural propagation of the epidemic is affected by implementations of (non-pharmaceutical) interventions. Successful implementation of such measures can favourably alter the path of the epidemic. The study proposes to implement such a model after adding extra features that are pertinent to the Indian subcontinent. A third aspect of COVID-19 is predicting the aftermath of the pandemic.
These models have been applied to Indian state-level data to describe and predict domestic COVID-19 situation and these developed models will help to train other scientists for capacity building for future problems.
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Modeling geographical spread of COVID-19 in India using networkbased approach
Most of the existing epidemiological models consider a closed environment. There is hardly any approach that considers network dynamics that happen between the geographic locations that are encountered by the model.
The project is aimed to predict the spread of COVID-19 in India under the assumption that migration happens between States. The objective is to model the spread of COVID-19 in the different States of India with inter-State migration allowed. As there are limited such attempts and they do not provide any concrete mathematical model, so the contribution will be novel.
It is observed that the proposed model is more intuitive than being mathematically effective. The preliminary theoretical study suggested pursuing a more robust model for understanding disease progression. This model suggests weighting the population variables.
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A collaborative study by the labs of NCBS, DBT and CSIR on the entry of Coronavirus into cells and leveraging existing drugs to combat viral entry and infections
In the wake of COVID-19, there was a pivot in the focus of several labs. Collaborations were born to apply the hard-won skills, techniques and knowledge from various labs to study the viral infection process and potential therapeutics.
Year 2020 saw the start of a large interinstitutional effort between labs on the campus, and the Indian Institute of Integrative Medicine (CSIR-IIIM), fuelled by the desire to combine the expertise of diverse scientists towards alleviating the global challenges of the pandemic we continue to face. In this effort, a large team came together to identify entry mechanisms of SARS-CoV-2 into cells and strategies to inhibit the infections by targeting those mechanisms.
The mechanism of entry into the cell, or ‘endocytosis’, happens through the formation of an ‘endosome’ or vesicle from the cell membrane. Investigating the pathway of entry showed them a requirement for viral entry: the acidified endosomes. This led them to the identification of agents to inhibit acidification of endosomes and thus affect viral infection.
The experiments began with the simplest probe, and the probes’ complexity grew. With their experience in endocytic work, researchers focused on the cell entry process using the receptor binding domain (RBD) of SARS-CoV-2 spike protein. They found that both endocytic pathways utilised by the RBD (with and without ACE2 receptor) converge on acidified endosomes. This, therefore, may be a requirement for virus entry. They also used this pseudovirus to test ways to inhibit viral entry. The experiments with the RBD protein and pseudovirus entry into the cells offered many insights, including controlling the acidification of the endosome to prevent viral entry. The testing of the efficacy of Niclosamide and other inhibitors on the real SARS-CoV-2 was possible once approvals and transfers were in place for clinical samples to be used in the investigation.
Study on alternations in immune, inflammatory and endocrine responses in Indian diabetic patients infected with SARS-CoV-2 and its clinical consequences
Dr. Saroj Kumar Sahoo from Sanjay Gandhi Postgraduate Institute of Medical Sciences is conducting a study on the immune and endocrine stress response in COVID-19 patients with and without diabetes. The purpose of the study is to estimate whether a higher viral load contributes to poor prognosis in patients with Diabetes Mellitus (DM). This study will also provide new information on the endocrinological spectrum of manifestations of COVID-19 such as new-onset DM, pituitary, adrenal, and thyroid disorders. Some of the disorders like adrenal insufficiency, if detected in a timely manner can be lifesaving when treated adequately. This study will help in understanding the pathophysiology of severe illness in patients with DM and thus will help in designing a strategy for better monitoring, risk-stratification, and management in patients with DM infected with SARS-CoV-2.
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COVID-19 lung ultrasound database: A study by IIT Palakkad
Dr. Mahesh Raveendranatha Panicker and his team from the Indian Institute of Technology (IIT) Palakkad, has done a study on the COVID-19 lung ultrasound (LUS) of 1500 data with the help of a lightweight algorithm. This algorithm ‘you look only once’ version 5 (YOLO5) and single-shot detection (SSD) has the capability of providing quality images based on the identification of various LUS landmarks, prediction of severity of lung infection, and so on. Also there is the possibility of active learning through this database based on the feedback from clinicians.
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Understanding the efficacy of existing drug molecules on COVID-19 through an interactive pathway: A deep learning-based predictive model
The faculty of Indian Statistical Institute, Kolkata, Prof. Rajat Kumar De has done a study to identify the potential bioactive drug candidates and allow further investigation of the molecular mechanisms of action. In this research, the role of artificial intelligence (AI) in the identification, diagnosis and spread of SARS-CoV-2 virus has been studied. It is observed that AI-based image processing techniques had a colossal application in the detection of COVID-19 pneumonia in patients, based on chest X-ray, chest computed tomography (CT) and chest high resolution computed tomography (HRTC) images. Further, AI-based predictive models had shown potential in the identification of effective drugs molecules, repurposing of which might help in the treatment of COVID-19 disease. Based on literature reviews and an autoencoder-based deep learning methodology, Mozenavir, Oseltamivir and Di-hydro-artemisinin has been identified as probable drug molecules that might be effective in the treatment of SARS-CoV-2 virus. The available structure of SARS-CoV-2 virus has also been analysed and through knowledge-based docking, probable binding sites for vitamin D3 and ivermectin identified. It thus opens up new avenues for repurposing of these drug molecules as potential drugs against SARS-CoV-2 viral infection.
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Study on SARS-CoV-2 Delta variant replication and immune evasion mechanism
In an international collaboration involving CSIR-IGIB and INSACOG consortium and others, a group of researchers examined the underlying mechanisms for SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.
The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha). The study suggests that the Delta variant is six-fold less sensitive to serum neutralising antibodies from recovered individuals, and eight-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G.
The Delta variant demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to Alpha variant. The Delta variant spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralising antibody as compared to WT spike. Additionally, it was observed that Delta variant had higher replication and spike mediated entry as compared to Kappa variant, which explains the dominance of Delta variant mediated infections. The study has been published in Nature.
IIT Delhi, AIIMS New Delhi and Addverb co-develop telerobotic ultrasound system during COVID-19 pandemic times
Research collaboration between IIT Delhi and AIIMS New Delhi, jointly developed a telerobotic ultrasound system.
The system allows remote ultrasound access through a robotic arm. In the routine ultrasound setting, the doctor (radiologist) stands in close contact with the patient for the entire duration of the scan. However, cross-sectional imaging is preferred instead in the current pandemic scenario with stringent social distancing requirements – a more expensive and less dynamic technique. Ultrasonography is a non-invasive, non-ionizing, cost-effective, rapid, bedside, and readily available modality with immense use in point-of-care and followup examinations.
The research team at IIT Delhi was led by Prof. Chetan Arora and Prof. Subir Kumar Saha. Dr. Chandrashekhara from AIIMS made this system. Mr. Suvayan Nandi was the lead contributor from Addverb Technologies.
This system will promote health care and make the system more prepared for further pandemics. Besides its role in the pandemic, it will allow a better outreach of ultrasound imaging to remote rural areas of India. The radiologist manipulates the ultrasound probe remotely from a remote location, acquires the ultrasonographs, and then transmits them to the monitors at the doctor’s end through a Wi-Fi network. Sitting at a remote location, the doctor can view all the images and assess the patient, similar to a clinical setting. The facility can also be extended for global outreach.
Website link: https://home.iitd.ac.in/show.php?id=37&in_sections=Press
Study on the impact of environmental indicators on the COVID-19 pandemic in Delhi
Currently, there is a massive debate on whether meteorological and air quality parameters play a crucial role in the transmission of COVID-19 across the globe. With this background, an IIT Indore study aims to evaluate the impact of air pollutants (PM2.5, PM10, CO, NO, NO2 , and O3) and meteorological parameters (temperature, humidity, wind speed, and rainfall) on the spread and mortality due to the COVID-19 outbreak in Delhi from 14 March 2020 to 3 May 2021. The Spearman’s rank correlation method employed on secondary data shows a significant correlation between the COVID-19 incidences and the PM2.5, PM10, CO, NO, NO2, and O3 concentrations. Amongst the four meteorological parameters, temperature is strongly correlated with COVID-19 infections and deaths during the three phases, i.e., pre-lockdown (14 March 2020 to 24 March 2020) (r = 0.79), lockdown (25 March 2020 to 31 May 2020) (r = 0.87), and unlock (1 June 2020 to 3 May 2021) (r = −0.75), explaining the variability of about 20-30 per cent in the lockdown period and 18-19 per cent in the unlock period. NO2 explained the maximum variability of 10 per cent and 7 per cent in the total confirmed cases and deaths among the air pollutants, respectively. A generalised linear model could explain 80 per cent and 71 per cent of the variability in confirmed cases and deaths during the lockdown and 82 per cent and 81 per cent variability in the unlock phase, respectively. These findings suggest that these factors may contribute to the transmission of COVID-19 and its associated deaths. The study results would enhance the ongoing research related to the influence of environmental factors. They would be helpful for policymakers in managing the outbreak of COVID-19 in Delhi, India.
Website link: https://www.mdpi.com/2076-0817/10/8/1003/htm
COVID-19 pandemic: Insights into molecular mechanisms leading to sex-based differences in patient outcomes
Recent epidemiological studies analysing sex-disaggregated patient data of coronavirus disease 2019 (COVID-19) across the world revealed a distinct sex bias in the disease morbidity as well as the mortality – both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of molecular mechanisms leading to the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex-differentiated approach for therapeutic management of this disease. Recent studies that have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce.
However, existing evidence, for other respiratory viral infections, viz. SARS, MERS and influenza, provides important clues in this regard. In an attempt to consolidate the available knowledge on this issue, a group of researchers from Etiologically Elusive Disorders Research Network (EEDRN), AIIMS Patna, and IIT Gandhinagar conducted a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as evolutionary and genetic/ epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome-mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19.
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IIT Palakkad made a roadmap for investigation on the long-term effects of COVID-19 in the context of airways diseases
As we all know the long-term effects of COVID-19 in the recovered patients are not yet elaborated. Prof. Jagadeesh Bayry is a part of the international consortium to identify research priorities to understand the long-term sequelae of COVID-19 in the population with preexisting and new on-set airways diseases including chronic obstructive pulmonary disease and asthma. The consortium has identified the prognosis scores as the main area of future investigation. Emphasis was also laid on the prevalence and severity of post-COVID-19 fatigue, anxiety, depression, and risk of cardiovascular complications in such patients.
Second round statewide survey for estimation of the burden of active infection and anti-SARS-CoV-2 IgG antibodies in the general population of Karnataka, India
The second round of the serial cross-sectional sentinel based population survey to assess active infection, sero-prevalence, and their evolution in the general population across Karnataka was conducted. Additionally, a longitudinal study among participants identified as COVID-19 positive in the first survey round was conducted to assess the clinical sensitivity of the testing kit used. Methods: The cross-sectional study of 41,228 participants across 290 health care facilities in all 30 districts of Karnataka was done among three groups of participants (low, moderate, and high risk). Consenting participants were subjected to real time reverse transcription-polymerase chain reaction (RT-PCR) testing, and antibody (IgG) testing. Results: Overall weighted adjusted seroprevalence of IgG was 15.6 per cent (95% CI: 14.9 to 16.3), crude IgG prevalence was 15.0 per cent and crude active prevalence was 0.5 per cent. Statewide infection fatality rate (IFR) was estimated as 0.11 per cent, and COVID-19 burden was estimated between 26.1 to 37.7 per cent (at 90% confidence). Clinical sensitivity of the IgG ELISA test kit was estimated as equal or more than 38.9 per cent. Conclusion: The sentinel-based population survey helped identify districts that needed better testing, reporting, and clinical management. The State was far from attaining natural immunity during the survey and hence must step up vaccination coverage and enforce public health measures to prevent the spread of COVID-19.
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Website link: https://covid19.iisc.ac.in/second-round-statewide-survey-for-estimation-of-the-burden-of-active-infection-and-anti-sars-cov-2-igg-antibodies-in-the-general-population-of-karnataka-india/
Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples
While vaccine development for COVID-19 has progressed rapidly, the discovery of prognostic markers and antiviral drugs has been lagging behind. Several research groups have examined the host response in the respiratory tract to SARS-CoV-2 infection using OMICs technologies and large amounts of big data have been generated. Careful analysis of these data can provide insights required for COVID-19 prognosis and antiviral development.
A recent study, led by Shashank Tripathi from the Centre for Infectious Diseases Research and published in EbioMedicine, reports two novel findings: a specific gene signature in nasal swabs, which can predict COVID-19 severity, and the potential offered by an FDA-approved drug (Auranofin) for COVID-19 therapy.
Current methods of assessing COVID-19 severity involve drawing blood or imaging the chest, both of which require a hospital visit. In the study, the researchers conducted a meta-analysis of COVID-19 OMICs data from nasopharyngeal samples, which revealed host factors that are consistently upregulated during infection. They were able to identify specific genes belonging to the S100 family (S100A6, S100A8, S100A9, and S100P), which could serve as prognostic markers of severe COVID-19. This gene signature can be detected by RT-PCR in the nasal swabs, which are collected for COVID-19 diagnosis.
In the study, the researchers also identified multiple host processes, which may be involved in virus replication and disease progression, and may serve as targets for host-directed therapy. Crucially, a redox regulatory protein called Thioredoxin (TXN) was found to be consistently upregulated in COVID-19 patients. Auranofin, an FDA-approved drug that targets the enzyme thioredoxin reductase and blocks the thioredoxin pathway, was found to mitigate SARS-CoV-2 replication in cell culture as well as in the preclinical Syrian hamster model. Auranofin is a safe and economical drug used for arthritis treatment. The study, therefore, suggests that it could serve as a promising COVID-19 antiviral.
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Fighting COVID-19 viral variants with a heat-tolerant vaccine
A ‘warm’ COVID-19 vaccine candidate being developed by an Indian Institute of Science (IISc), Bengaluru and Mynvax team was found to trigger a strong immune response and protection in mice and hamster models, in results published recently in ACS Infectious Diseases. Crucially, the vaccine formulation also triggered neutralising antibodies – those that bind to the virus and prevent infection – against all four current SARS-CoV-2 variants of concern: Alpha, Beta, Gamma and Delta.
The vaccinated sera (blood) samples from animal models were tested for their neutralising ability against the variants by researchers at CSIR-IMTech, Chandigarh and the Australian Centre for Disease Preparedness, run by CSIRO, Australia’s national science agency.
The vaccine candidate has been designed by genetically engineering a domain of the surface spike glycoprotein of SARS-CoV-2, called the Receptor Binding Domain (RBD), which plays a key role in facilitating viral entry and infection. Most of the neutralising antibodies produced by our body, target the RBD.
In previous reports, an earlier version of the vaccine candidate was found to be stable at 37°C for a month without losing its shape, and withstand transient exposure to temperatures as high as 100°C. This was also true of the current, improved versions. Such vaccines are especially useful in countries like India where cold storage and transportation are expensive and challenging. One of the improved formulations is being rapidly moved to clinical development.
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Fighting COVID-19 viral variants with a heat-tolerant vaccine
A ‘warm’ COVID-19 vaccine candidate being developed by an Indian Institute of Science (IISc) and Mynvax team was found to trigger a strong immune response and protection in mice and hamster models. These results were recently published in ACS Infectious Diseases. Crucially, the vaccine formulation also triggered neutralising antibodies – those that bind to the virus and prevent infection – against all four current SARS-CoV-2 variants of concern: Alpha, Beta, Gamma and Delta.
The vaccinated sera (blood) samples from animal models were tested for their neutralising ability against the variants by researchers at CSIR-IMTech, Chandigarh and the Australian Centre for Disease Preparedness, run by CSIRO, Australia’s national science agency.
The vaccine candidate has been designed by genetically engineering a domain of the surface spike glycoprotein of SARS-CoV-2, called the Receptor Binding Domain (RBD), which plays a key role in facilitating viral entry and infection. Most of the neutralising antibodies produced by our body target the RBD.
In previous reports, an earlier version of the vaccine candidate was found to be stable at 37oC for a month without losing its shape, and withstand transient exposure to temperatures as high as 100oC. This was also true of the current, improved versions. Such vaccines are especially useful in countries like India where cold storage and transportation are expensive and challenging. One of the improved formulations is being rapidly moved to clinical development.
NIAB hunts for PAN-Anti-CoronAvirals (PANACeA) against coronaviruses of the past, present and future
The National Institute of Animal Biotechnology (NIAB) collaborates with THSTI to test antivirals without culturing coronaviruses. The idea is to make the backbone of coronaviruses artificially without critical elements essential for virus replication. The system can be used for screening multiple compounds simultaneously, against coronaviruses of all time – past, present and future.
It aims to facilitate faster progression for the identification of potential compounds through rapid preliminary screening of several compounds.
IISc receives ILSF grant for developing mRNA vaccine technology
A team of researchers from IISc has received a grant from the Ignite Life Science Foundation (ILSF) to develop platform technologies for mRNA vaccine development. The team comprises Prof Raghavan Varadarajan, Prof Mrinmoy De and Prof Siddharth Jhunjhunwala from IISc, as well as Dr Amit Awasthi at the Translational Health Science and Technology Institute (THSTI) Faridabad. The investigators will attempt to develop methods for the generation of thermostable RNA vaccines, including variants of SARS-Cov-2, which would be critical for resource poor tropical regions of the world.
ILSF, a Section 8 not-for-profit, was launched in 2020 by Nobel Laureate Dr Venki Ramakrishnan. It aims to promote a vibrant ecosystem for scientific research in India.
inStem developing natural antimicrobial peptides (AMP) for antiviral immunity
The Institute for Stem Cell Science and Regenerative Medicine (inStem), an autonomous institute of Department of Biotechnology (DBT), is exploring if the body’s immune system can be harnessed to block or protect from SARS-CoV-2 infection. A specific class of molecules of the immune system called antimicrobial peptides (AMPs), produced in many parts of the body, form the focus of this effort. The hypothesis that AMPs are likewise capable of killing the virus that causes COVID-19 is being tested. These AMPs have the potential to block the initial infection and could, if practical, limit the spread of the virus in people already infected to reduce the severity of the disease.
This approach will be an additional level of protection along with COVID-19 appropriate behaviour. Additionally, it would complement the vaccines currently being administered (or in development) to help combat viral strains potentially mutated to decrease the vaccine’s efficacy.
Contact info: Colin Jamora (email@example.com)
NIBMG, in collaboration with IISc, is developing a novel virus-like particle vaccine against coronavirus
National Institute of Biomedical Genomics (NIBMG), an autonomous institute of DBT, in collaboration with IISc, is working on a project to design virus-like particles (VLP) specific to the Indian strain of SARS-CoV-2 and further study the possibility of development of a vaccine against the SARS-CoV-2 virus using the same.
Contact info: Saumitra Das (firstname.lastname@example.org)
CIAB developing photodynamic therapy as an antiviral treatment for the eradication of SARS-CoV-2
A team of researchers from the Center of Innovative and Applied Bioprocessing (CIAB) is developing a series of photosensitiser nano formulations. One formulation showed very high efficacy (equivalent to Ramdesivir) to destroy SARS-Cov-2 in vitro.
Contact info: Jayeeta Bhaumik (email@example.com)
ICGEB working on human monoclonal antibodies for prevention and treatment of COVID-19
Human monoclonal antibodies have the potential to be used for both prevention and treatment of infection. Over 200 human monoclonal antibodies from single-cell sorted memory B cells derived from COVID-19 recovered individuals in India have been generated and analysed for their neutralising activity on SARS-CoV-2. Several potent neutralisers have been identified.
This work showed that nearly half of the COVID-19 recovered individuals developed neutralising antibodies. These individuals can be identified by simple to use SARS-CoV-2 RBD ELISA’s. The work is being done by ICGEB in collaboration with NIMR-ICMR and Emory University
Contact info: Dr Anmol Chandele (firstname.lastname@example.org)
RGCB, Thiruvananthapuram is working on new therapeutics against SARS-CoV-2
Rajiv Gandhi Centre for Biotechnology (RGCB) establishes cell-based assays targeting viral entry mediated by the spike protein and evaluates the functional activity of viral main protease (Mpro), also known as 3C-like protease (3CLPro). Also, these assays are being used to identify potential hits by screening newly in-house synthesised small molecules, focusing on entry inhibitors that are derivatives of Arbidol.
The project aims to develop cell-based assays to identify inhibitors of SARS-CoV-2 entry and inhibitors of viral protease. It also plans to screen derivatives of Arbidol as virus entry inhibitors. The results will lead to the subsequent development of potential drug candidates against COVID-19.
Contact info: email@example.com
IIT Indore in collaboration with NCCS pseudotyped SARS-CoV-2 in BSL-2 for candidate vaccine development
With the development of the COVID-19 pandemic, there is an urgent need to establish a system for determining the effectiveness and neutralising activity of vaccine candidates in biosafety level 2 (BSL-2) facilities. IIT Indore, in collaboration with NCCS-Pune set the pseudovirus production. Mice were immunised with the pseudovirus, and their antibody response was tested. The research initiative is being supported by Biotechnology Industry Research Assistance Council (BIRAC). The research outcome is expected to help in vaccine development.
Contact info: Dr Akanksha Chaturvedi (firstname.lastname@example.org)
Generation of virus-neutralising human monoclonal antibodies (hmABs) against SARS-CoV-2 as potential therapeutics
National Centre for Cell Science (NCCS), in partnership with IIT Indore, PredOmix Technologies Pvt. Ltd., Bharat Biotech International Ltd. (BBIL) and AFMC, Pune is working on virus-neutralising human monoclonal antibodies (hmABs) against SARS-CoV-2 as potential therapeutics.
Serum samples from patients are being screened for the presence of antibodies that specifically bind to the receptor-binding domain (RBD) of the virus. B cells grown and selected B cell clones are being tested for specific antibodies against the RBD. Of the approximately 150 B cell clones obtained in the lab, two were transferred to BBIL earlier for further development. The neutralisation efficacy of other potent clones is being analysed at IIT Indore. Supernatant from these clones was transferred to Bharat Biotech International Limited (BBIL) to test for virus neutralisation. Almost 10 other clones showed neutralisation with the actual virus, which is being characterised further.
Contact info: Dr Arvind Sahu (email@example.com)
NIPGR working on a platform for producing COVID-19 related antigens and antiviral proteins through transient expression in plants
Researchers from National Institute of Plant Genome Research (NIPGR) are working on a plant vaccine to help in controlling the coronavirus infection. Compared to conventional vaccination processes, the recombinant vaccines produced in plants are heat stable, lack animal pathogen contamination, are economically practical, and can be made in large amounts. The target is to produce an experimental plant-based vaccine for COVID-19 against S-glycoprotein protein of coronavirus.
Contact info: Dr Manoj Prasad (firstname.lastname@example.org)
Examining the potential for use of natural plant products, flavonoids, against SARS-CoV-2
To tackle the pandemic, there is an immediate need to find a therapeutic against SARS-CoV-2. NIPGR contributes to research preparedness in the fight against this virus. Dr Ashutosh Pandey and his team from NIPGR are working to find drugs against SARS-CoV-2. The group is rigorously involved in exploring natural plant products, specifically flavonoids that are potentially antiviral. The potential activity of the identified molecule/s against SARS-CoV-2 will be tested in collaboration with Regional Centre for Biotechnology (RCB), Faridabad.
Contact info: Dr Ashutosh Pandey (email@example.com)
Immune memory in mild COVID-19 patients and unexposed donors reveals persistent T cell responses after SARS-CoV-2 infection
Understanding the causes of the diverse outcome of the COVID-19 pandemic in different geographical locations is essential for the worldwide vaccine implementation and pandemic control responses. A research study conducted at National Institute of Immunology (NII) analysed 42 unexposed healthy donors and 28 mild COVID-19 subjects up to five months from recovery for SARS-CoV-2 specific immunological memory. Using HLA class II predicted peptide megapools, SARS-CoV-2 cross-reactive CD4+ T cells were identified in around 66 per cent of the unexposed individuals. Moreover, detectable immune memory was found in mild COVID-19 patients several months after recovery in the crucial arms of protective adaptive immunity, CD4+ T cells and B cells, with a minimal contribution from CD8+ T cells.
Interestingly, the persistent immune memory in COVID-19 patients is predominantly targeted towards the Spike glycoprotein of SARS-CoV-2. The NII study provides evidence of high magnitude pre-existing and persistent immune memory in the Indian population. By providing the knowledge on cellular immune responses to SARS-CoV-2, work implies the development and implementation of vaccines against COVID-19.
Contact info: Dr Nimesh Gupta (firstname.lastname@example.org)
NII working on identification of potential anti-COVID-19 compounds targeting the RNA dependent RNA polymerases
Aiming to identify anti-COVID-19 compounds, researchers from NII have found that using structural and biochemical approaches, three widely used kinase inhibitors (sorafenib, sunitinib, and SU6656) significantly circumvent the kinase-like activity exhibited by the NiRAN domain of SARS-CoV-2 RdRP.
The fundamental research on an essential drug target (viral polymerase) has led to identifying a novel small molecule with anti-COVID-19 activity. Thus, this may find application in COVID-19 treatment.
Contact info: Dr Bichitra K Biswal (email@example.com)
IIT Mandi reveals the structure of a key protein in the COVID-19 virus in the host cell environment
A team of researchers from IIT Mandi, led by Dr Rajanish Giri has elucidated the structure of a key protein in the COVID-19 virus. This helps in understanding its mode of action, its role in the spread and severity of the disease and development of antiviral therapeutics.
The team has experimentally studied the structural conformations of SARS-CoV-2 NSP1 under various conditions – in an organic solvent, membrane mimetic environment, and inside liposomes. Using various analytical techniques and molecular dynamic simulations, the researchers have shown the dynamic changes in the conformation of the IDR of the NSP1, in response to its surroundings, due to hydrophobic and electrostatic interactions between the protein and the environment.
Plant derived active compounds as potential anti SARS-CoV-2 agents, finds an in-silico study by IIT Indore
Plants are a valued potential source of drugs for a variety of diseases and are often considered less toxic to humans. Antiviral compounds that may potentially target SARS-CoV-2 antigenic spike (S) and host proteins – angiotensin-converting enzyme2 (ACE2), and transmembrane serine protease2 (TMPRSS2) – were invested; and 36 phytochemicals were scrutinised from 15 Indian medicinal plants known to be effective against RNA viruses via molecular docking. Besides, the TMPRSS2 structure was modelled and validated using the SWISSMODEL. Docking was performed using AutoDock Vina and 4.2 followed by visualisation of the docking poses on Pymol version 2.4.0 and Discovery Studio Visualizer. Molecular docking showed that 12 out of 36 active compounds interacted efficiently with S, ACE2, and TMPRSS2 proteins. The ADMET profile generated, using the swissADME and pkCSM server, revealed that these compounds possessed druggable properties. The Amber 12 simulation package was used to carry out energy minimisations and molecular dynamics (MD) simulations. The total simulation time for both S protein – WFA and S protein – WND complexes was 300 ns (100 ns per replica). A total of 120 structures were extracted from the last 60 ns of each MD simulation for further analysis. MM-PBSA and MM-GBSA were employed to assess the binding energy of each ligand and the receptor-binding domain of the viral S-protein. The methods suggested that WND and WFA showed thermodynamically favourable binding energies, and the S protein had a higher affinity with WND. Interestingly, Leu455 hotspot residue in the S protein, also predicted to participate in binding with ACE2, was engaged by WND and WFA.
IIT Patna has developed a deep learning empowered COVID-19 diagnosis technology using chest CT scan images for collaborative edge cloud computing platform
The novel coronavirus outbreak has spread worldwide, causing respiratory infections in humans, leading to a huge global pandemic COVID-19. According to WHO, the only way to curb this spread is by increasing the testing and isolating the infected. Meanwhile, the clinical testing currently being followed is not easily accessible and requires time to give the results.
In this scenario, remote diagnostic systems could be a handy solution. Some existing studies leverage the deep learning approach to provide an effective alternative to clinical diagnostic techniques. However, it is difficult to use such complex networks in resource constraint environments. To address this problem, a fine-tuned deep learning model inspired by the architecture of the MobileNetV2 model has been developed. The developed model is further optimised in terms of its size and complexity to make it compatible with mobile and edge devices. The results of extensive experimentation performed on a real-world dataset consisting of 2482 chest computerised tomography scan images strongly suggest the superiority of the developed fine-tuned deep learning model in terms of high accuracy and faster diagnosis time. The proposed model has achieved a classification accuracy of 96.40 per cent, with approximately 10 times shorter response time than the prevailing deep learning models. Further, McNemar’s statistical test results also prove the efficacy of the proposed model.
An update on antiviral therapy against SARS-CoV-2: An IIT Indore study
Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARSCoV-2 candidates. Several of them are either, antimalarials, antivirals, antibiotics or corticosteroids. They have been repurposed based on their potential to negate virus or reduce lung inflammation. A large number of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs, of which a few clinical studies are complete, the results of which are primary. World Health Organization (WHO) also conducted an international, multi-country, open-label, randomised trial, which was a solidarity trial for four antiviral drugs. However, solidarity trials have a few limitations: no placebos used, any drug may show effectiveness for a particular population in a region, which may get neglected in solidarity trial analysis, etc. The ongoing randomised clinical trials can provide a reliable long-term follow-up result that will establish both clinical safety and efficacy of these drugs with respect to different regions, populations and may aid worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARSCoV-2. The review also summarises the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the pre-clinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.
Tissue engineering and its significance in healthcare during the COVID-19 pandemic: Potential applications and perspectives
There is a great need for new therapeutic and diagnostic strategies to prevent infectious diseases worldwide. Tissue engineering covers the phenomenon of the evolution of tissue, its behaviour and growth factors that are better supported in the medical environment. This area of tissue engineering can support the treatment of COVID-19 patients and can help fight the current crisis and viral outbreaks in general.
This study aims to identify the significant advancement in tissue engineering for taking up challenges posed by COVID-19. The study discusses the major challenges faced during the pandemic, lists the significant advancements of tissue engineering in the medical field in a chronological order, discusses the positive impact of tissue engineering and finally, identifies and briefs its useful application during the ongoing pandemic situation. The primary importance of this branch of science is to provide biological alternatives that can perform full or partial functions of the damaged, malfunctioned and failing organs or tissues in humans. It is helpful for the supply of convalescent plasma to patients especially during COVID-19. A donor is selected strictly based on a validated case of COVID-19 contagion. The donor must confirm a negative follow-up molecular examination, free from manifestations. The usual good health and other pre-donation screening procedures are to be followed.
IIT Indore performs mutational analysis of structural proteins of SARS-CoV-2
SARS-CoV-2 transmissibility is higher than that of other human coronaviruses. Therefore, it poses a threat to the populated communities. Mutations among envelope (E), membrane (M), and spike (S) proteins from different isolates of SARS-CoV-2 and plausible signalling influenced by mutated virus in a host was investigated. Updated protein sequences from the NCBI virus database were procured. Mutations were analysed in the retrieved sequences of the viral proteins through multiple sequence alignment. Additionally, the data was subjected to ScanPROSITE to analyse if the mutations generated a relevant sequence for host signalling. Unique mutations in E, M, and S proteins resulted in modification sites like PKC phosphorylation and N-myristoylation sites. Based on a structural analysis, the study revealed that the D614G mutation in the S protein diminished the interaction with T859 and K854 of adjacent chains. Moreover, the S protein of SARS-CoV-2 consists of an Arg-Gly-Asp (RGD) tripeptide sequence, which could potentially interact with various members of the integrin family receptors. RGD sequence in S protein might aid in the initial virus attachment. Crucial host pathways, which the mutated isolates of SARS-CoV-2 may alter like PKC, Src, and integrin mediated signalling pathways, were speculated. PKC signalling is known to influence the caveosome/raft pathway, which is critical for virus entry. Additionally, the myristoylated proteins might activate NF-kB, a master molecule of inflammation. Thus the mutations may contribute to the disease pathogenesis and distinct lung pathophysiological changes. Further, the frequently occurring mutations in the protein can be studied for possible therapeutic interventions.
IIT Indore studies insights into Plasmodium and SARS-CoV-2 co-infection driven neurological manifestations
In malaria-endemic regions, people often get exposed to various pathogens simultaneously, generating co-infection scenarios. In such scenarios, overlapping symptoms pose serious diagnostic challenges. The delayed diagnosis may lead to an increase in disease severity and catastrophic events. The COVID-19 pandemic caused by SARS-CoV-2 has affected various areas globally, including malaria-endemic regions. The Plasmodium and SARS-CoV-2 co-infection and its effect on health are yet unexplored. The National Institute of Technology (NIT) Jalandhar has presented a case report of a previously healthy, middle-aged individual from the malariaendemic area who suffered SARS-CoV-2 and Plasmodium falciparum co-infection. The patient developed severe disease indications in a short time period. The patient showed neurological symptoms, altered haematological as well as liver-test parameters, which resulted in subsequent death in a short time span. NIT Jalandhar discussed the various aspects of this case regarding the treatment and haematological parameters. Further, NIT Jalandhar has also put forward perspectives related to the mechanism behind severity and neurological symptoms in this fatal parasite-virus co-infection case. In malaria-endemic regions, due to overlapping symptoms, suspected COVID-19 patients should also be monitored for diagnosis of malaria without any delay. The SARS-CoV-2 and Plasmodium co-infection could increase the disease severity in a short time span. In treatment, dexamethasone may not help in a severe case that has malaria as well as COVID-19 positive status. This will need further exploration.
Cloud computing to solve problems of COVID-19 pandemic
Cloud computing facilitates collaboration, communication, and essential online services during the COVID-19 crisis. The current situation of the COVID-19 pandemic has compelled people to work from their homes, but they have to communicate and collaborate online. Thus, researchers from NIT Jalandhar see an essential role of cloud computing in taking up this challenge of working from home and delivering efficiently. A brief review of cloud computing service in the context of COVID-19 pandemic has been done using recent papers by searching keywords such as ‘cloud computing’ and ‘COVID-19’ from PubMed’s database SCOPUS and Google Scholar. During the lockdown situation, cloud computing technology helped provide commendable service in the healthcare domain. It provides an advanced infrastructure for facilitating digital transformation. A brief discussion has been initiated on how cloud computing components are vital for overcoming the ongoing situation. This paper also studies the remote working of cloud computing for the COVID-19 pandemic and finally it also identifies significant cloud computing applications for the COVID-19 pandemic. All countries are focussed on reducing this virus’s spread. So, this technology helps minimise the spread of this virus by providing online services. It provides an innovative environment that enhances the creativity and productivity of healthcare workers. This technology is efficient in detecting, tracking, and monitoring newly infected patients. In the future, this technology will insight and provide control over this infection to save millions of lives worldwide. This technology is also quite helpful to forecast the future impact of the SARS-CoV-2 virus.
Advancements in biosensor technologies for medical field and COVID-19 pandemic: A study by NIT Jalandhar
The World Health Organization (WHO) declared the COVID-19 outbreak as a public health emergency of international concern and then as a pandemic on 30 January and 11 March 2020, respectively. After such concern, the world scientific communities have rushed to search for solutions to bring down the disease’s spread, fast-paced vaccine development, and associated medical research using modern technologies. Biosensor technologies play a crucial role in diagnosing various medical diseases, including COVID-19. The present paper describes the major advancement of biosensor-based technological solutions for medical diagnosis, including COVID-19. This review-based work covers the biosensors and their working principles in the context of medical applications. The paper also discusses different biosensors and their applications to tackle medical issues, including this ongoing pandemic.
How artificial intelligence and internet of things (IoT) can aid in the distribution of COVID-19 vaccines: A perspective
Prior to the COVID-19 pandemic, challenges related to our aging population and a shortage of healthcare professionals had already accelerated the deployment of artificial intelligence (AI) in healthcare. This trend has been hastened by the pandemic. Real time contact tracing applications are only one of the many AI applications being used to control the virus’s spread and bolster public health response. Since the beginning of the COVID-19 crisis, artificial intelligence and the internet of things (IoT) have played an important role, convincing that they can be very useful tools in dealing with this type of crisis. As the world begins to get vaccinated against COVID-19, some important logistics and access questions arise. Indeed, in a country like India, where there are more than 1.3 billion people and limited resources, distributing the COVID-19 vaccine to the people can be a difficult task. The Indian government has approved two COVID-19 vaccines (Oxford-AstraZeneca’s Covishield and Bharat Biotech’s Covaxin), and the challenge of administering the two-dose vaccine to everyone will be a massive task.
In the first phase of India’s vaccination campaign, priority was given to all healthcare and frontline workers. In the second phase, which began on 1 March 2021, people over 60 and those between the ages of 45 and 59 who have specific co-morbidities were given the doses. In the third phase, from 1 April 2021, everyone over the age of 45, regardless of co-morbidity status, is eligible for vaccination. The majority of COVID-19 vaccines necessitate temperature controlled storage. For example, Oxford-AstraZeneca’s Covishield and Bharat Biotech’s Covaxin require a storage temperature of 2-80C. Sensor-based IoT technology, which enables continuous monitoring of data in real time, can be useful in ensuring an effective storage system. In the event of a temperature change, the sensors will read it and give a device warning for the next shipment of vaccines.
Furthermore, the whole process requires a large amount of data that must be handled and maintained in a cloud that is open to all stakeholders. The big issue is also monitoring real time details about the vaccine supply chain in remote areas of a country. The government can minimise this problem by using location-based analytics, which can assist in any form of vaccine supply chain problems.
IISc studies conformational flexibility and structural variability of SARS-CoV-2 S-protein
A research team from the Indian Institute of Science (IISc) has made a crucial breakthrough by successfully visualising different conformations or forms of the S protein of the SARS-CoV-2, the virus causing Covid-19, which exists in mainly two conformations: open and closed.
The work led by Somnath Dutta, assistant professor at the Molecular Biophysics Unit (MBU) of IISc has been published in Structure, a peer-reviewed scientific journal.
A salient feature of SARS-CoV-2 is the presence of the spike (S) proteins on the surface of the membrane that envelopes the genetic material of the virus. They appear as characteristic crown-like spikes on the viral surface. And, the S protein is significant for multiple reasons: It mediates the entry of the virus into the host cell and is also the site where neutralising antibodies produced by the host cells bind to the virus in order to inactivate it.
The team observed that around 68 per cent of the S proteins exist in open conformation at physiological pH 7.4, but their proportion decreases when the pH is slightly higher (pH 8.0) or lower (pH 6.5). This suggests that the interaction between the S protein and receptor is more favoured at physiological pH (pH 7.4) than on either side of the biological pH scale. The study will assist in developing novel therapeutic measures against SARS-CoV-2.
IIT Gandhinagar contributes in prevalence study of SARS-CoV-2 in communities through wastewater surveillance: A potential approach for estimation of disease burden
The episodic outbreak of COVID-19 due to SARS-CoV-2 is severely affecting the economy, and the global count of infected patients is increasing. The actual number of patients had been underestimated due to limited facilities for testing as well as the asymptomatic nature of the expression of COVID-19 on an individual basis. Tragically, for emerging economies with high population density, the situation has been more complex due to insufficient testing facilities for diagnosis of the disease. However, the recent reports about persistent shedding of viral RNA of SARS-CoV-2 in the human faeces have created a possibility to track the prevalence and trends of the disease in communities, known as wastewater-based epidemiology (WBE).
Antidrug resistance in the Indian ambient waters of Ahmedabad during the COVID-19 pandemic: An IIT Gandhinagar study
The ongoing COVID-19 pandemic increases the consumption of antimicrobial substances (ABS) due to the unavailability of approved vaccine(s). To assess the effect of imprudent consumption of ABS during the COVID-19 pandemic, IIT Gandhinagar has compared the 2020 prevalence of antidrug resistance (ADR) of Escherichia coli (E. coli) with a similar survey carried out in 2018 in Ahmedabad, India using SARS-CoV-2 gene detection as a marker of ABS usage. Researchers found a significant ADR increase in 2020 compared to 2018 in ambient water bodies, harbouring a higher incidence of ADR E.coli towards non-fluoroquinolone drugs. Effective SARS-CoV-2 genome copies were found to be associated with the ADR prevalence. The prevalence of ADR depends on the efficiency of WWTPs (wastewater treatment plants) and the catchment area in its vicinity. In the 2018 study, prevalence of ADR was discretely distributed, and the maximum ADR prevalence recorded was ~ 60 per cent; against the current homogenous ADR increase, and up to 85 per cent of maximum ADR among the incubated E.coli isolated from the river (Sabarmati) and lake (Chandola and Kankaria) samples. Furthermore, wastewater treatment plants showed less increase in comparison to the ambient waters, which eventually imply that although SARSCoV-2 genes and faecal pollution may be diluted in the ambient waters, as indicated by low Ctvalue and E.coli count, the danger of related aftermath like ADR increase cannot be nullified. Also, non-fluoroquinolone drugs exhibited overall more resistance than quinolone drugs. Overall, this is probably the first-ever study that traces the COVID-19 pandemic imprints on the prevalence of antidrug resistance (ADR) through wastewater surveillance and hints at monitoring escalation of other environmental health parameters. This study will make the public and policy holders concerned about the optimum use of antibiotics during any kind of treatment.
Coalescence of co-infection and antimicrobial resistance with SARS-CoV-2 infection: The blues of post-COVID-19 world
In viral respiratory infections, bacterial co-pathogens are widely known to co-infect, and they significantly increase the morbidity and mortality rate. During the influenza season, the advent of 2019-nCoV (novel coronavirus) has led to the widespread use of oral and intravenous antibiotics and inhibitors of neuraminidase enzyme. Owing to causes such as extended intubation, the ubiquitous use of intrusive catheters, and compromised host immunity, coronavirus disease (COVID-19) patients are at heightened risk of secondary bacterial and fungal infections, leading to difficulty in their treatment. Apart from the pandemic, the primary risk is a likely surge in multidrug resistance. In this work, IIT Gandhinagar evaluated the coalescence of the present co-infection along with the COVID-19 and post-pandemic antimicrobial resistance due to high ongoing drug use for the treatment of COVID-19. They found that while there is currently limited evidence of bacterial infections in COVID-19, available proof supports the restricted use of antibiotics from an antibiotic stewardship viewpoint, primarily upon entry. Paramount attempts should be made to collect sputum and blood culture samples as well as pneumococcal urinary antigen monitoring in order to endorse stringent antibiotic usage. For antimicrobial stewardship, inflammatory markers like procalcitonin have been added, but such biomarkers are typically upraised in COVID-19. Antimicrobials cannot be completely removed in WWTPs and once they enter the water environment, possesses a great risk of inducing resistance to drugs in microbes. Hence, their prescription and administration should be regulated and alternate solutions such as vaccines, preventive measures and personal hygiene should be given top priority. It is imperative to establish an antimicrobial strategy discrete to COVID-19, as this pandemic has caused an outbreak of numerous other associated diseases and has the potential to drive microbial resistance. Coordinated plans are essential for this at the citizen, healthcare and policy levels.
Immunological memory to SARS-CoV-2 in Indian population: Implications for design and implementation of vaccine
The COVID-19 pandemic has become a major threat to public health globally. In current scenario, vaccine is the most preferred preventive measures to protect from COVID-19. However, there are several questions that need to be answered for successful implementation of vaccine; particularly, (i) how long the vaccine will provide the protective cover; (ii) whether the vaccine will protect against all recently circulating and future variants of virus; and (iii) what should be the vaccination schedule and dosage for the individuals recovered from COVID-19. To answer these questions there is a need to investigate the underlying immunological determinants of protective immunity in COVID-19 patients in India.
Dr Nimesh Gupta’s group at the National Institute of Immunology (NII) is applying the advanced human T-cell immunology setup to address these questions in COVID-19 patients. The research program is actively progressing in multi-centric collaboration with Dr Ashok Sharma, Biochemistry Department and Dr Poonam Coshic, Department of Transfusion Medicine at the All India Institute of Medical Sciences (AIIMS), New Delhi. The research program is supported under the Intensification of Research in High Priority Areas (IRHPA) scheme of Science and Engineering Research Board (SERB), Department of Science and Technology, India.
A recent study from the group indicates that almost 70% of the examined Indian cohort has very high levels of SARS-CoV-2 reactive CD4+ T cells, which are present prior to the COVID-19 pandemic. These already present T cells strongly respond to the COVID-19 virus. Indeed, the pre-existing cross-reactive CD4+ T cells will not completely abort the virus infection but they can definitely limit the virus burden and reduce the course of symptomatic infection. This will lead to less severe disease and lower rates of hospitalization. These SARS-CoV-2 reactive CD4+ T cells may have originated due to previous exposure to the highly prevalent ‘Common Cold’ viruses.
This study also reveals that the Indian patients recovered from mild COVID-19 disease have durable immunological memory in most important arms of protective immunity – T cells and B cells. The team believes that such immunological memory should give protection at least for a few years. Interestingly, the memory CD4+ T cells and B cells in COVID-19 patients are predominantly associated with the spike protein of the virus. It’s a good sign. As these responses are mainly targeted towards the Spike protein, it also gives high hopes to the current vaccines. Because, if the vaccine can induce the immune response like seen in mild patients, then it will offer an effective and long-lasting cellular immunity against SARS-CoV-2. Moreover, this study suggests not to use virus nucleoprotein as the target protein for seroepidemiological surveys in India. It may give a wrong indication as almost 30% of the tested donors showed cross-reactive antibodies to SARS-CoV-2 nucleoprotein without the exposure to virus prior to pandemic
The study also hints that single-dose immunization with COVID vaccine may be sufficient to establish optimal protective responses in the individuals recovered from mild COVID-19. Thus, these findings are crucial in our understanding of how Indian population is responding to the COVID-19 virus. It also provides a key message for vaccine implementation in India.
Contact Info: firstname.lastname@example.org
Website link: https://doi.org/10.3389/fimmu.2021.636768
Repurposing drugs against main protease of SARS-CoV-2: Mechanismbased insights supported by available clinical data
The on-going global pandemic of COVID-19 has brought life to almost standstill with implementations of lockdown and social distancing as some of the preventive measures in the absence of any approved specific therapeutic interventions. To combat this crisis, research community world-wide are falling back on the existing repertoire of approved/ investigational drugs to probe into their anti-coronavirus properties. In a pre-print study by researchers at Indian Institute of Science (IISc), Bangalore have put unique efforts in identifying potential drugs that could be repurposed against main protease of SARS-CoV-2 (SARS-CoV-2 Mpro). To achieve this goal, the team primarily exploited the principles of ‘neighbourhood behaviour’ in protein 3-D (workflow-I) and chemical 2-D structural space (workflow-II) coupled with docking simulations and insights into the possible mode of actions of the selected candidates from available literature. Such an integrative approach culminated in prioritizing 29 potential repurposable agents (20 approved drugs and 9 investigational molecules) against SARS-CoV-2 Mpro. Apart from the approved/investigational anti-viral drugs, other notable hits include anti-bacterial, anti-inflammatory, anti-cancer and anti-coagulant drugs. The analysis suggests that some of these drugs have the potential to simultaneously modulate the functions of viral proteins and host response system. Interestingly, many of these identified candidates (12 molecules from workflow-I and several molecules belonging to the chemical classes of alkaloids, tetracyclines, peptidomimetics from workflow-II) are suggested to possess anti-viral properties which are supported by laboratory and clinical data. Further, this work opens a new avenue of research to probe into the molecular mechanism of action of many drugs which are known to demonstrate anti-viral activity but are so far not known to target viral proteases. The findings should only be used for research purposes and the team strongly urges that no individual should interpret these findings for any self-diagnosis or self-medication without the prior approval from competent international health/medical regulatory agencies.
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Neutralization potential of Covishield-vaccinated individuals’ sera against B.1.617.1
Covishield comprises the larger proportion in the vaccination programme in India. Hence, it is of utmost importance to understand neutralizing capability of vaccine against the B.1.617.1 variant which is considered to be responsible for surge of the cases in India. The neutralizingantibody (NAb) titer against B.1.167.1 and prototype B.1 variant (D614G) was determined of the vaccine sera (4 weeks after second dose) of COVID-19 naïve subjects (n=43) and COVID19-recovered subjects (n-18). The results demonstrated that sera of COVID-19 recovered subjects (n=18) who received two doses of Covishield have higher NAb response compared to the COVID-19 naive with a significant difference (p < 0.0001) in NAb titer against B.1 and B.1.617.1 In-spite of reduction in the neutralizing titer against B.1.617.1 variant, Covishield vaccine-induced antibodies are likely to be protective to limit the severity and mortality of the disease in the vaccinated individuals.
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Precipitation dynamics of surrogate respiratory sessile droplets leading to possible fomites
The on-going COVID-19 pandemic has disrupted global travel, healthcare systems, social interactions, and business activities. Primary transmission of the virus occurs at the microscale level, where respiratory droplets rapidly spread the SARS-CoV-2 among human beings. To arrest the transmission of the virus, wearing a facemask and maintaining social distances has been advised by the scientific and medical community worldwide. The ejected droplets are in the size range of 1–2000 um and create two possible scenarios of infection. Smaller droplets can evaporate, precipitate, travel far, and stay airborne for a sufficiently long time before being directly inspired by another healthy human being. On the other hand, the larger droplets may settle under gravity or impinge on a material surface, forming fomites. In either scenario, infection mechanics, which involve virus survivability, remains elusive. In an article, a team of researchers at IISC Bangalore has discussed the physicochemical transformations within a VEP (virus emulating particles)-loaded surrogate respiratory droplet drying on different commonly available real-life surfaces.
The droplets ejected from an infected host during expiratory events can get deposited as fomites on everyday use surfaces. Recognizing that these fomites can be a secondary route for disease transmission, exploring the deposition pattern of such sessile respiratory droplets on daily-use substrates thus becomes crucial.
The used surrogate respiratory fluid is composed of a water-based salt-protein solution, and its precipitation dynamics is studied on four different substrates (glass, ceramic, steel, and PET). For tracking the final deposition of viruses in these droplets, 100 nm VEP are used and their distribution in dried-out patterns is identified using fluorescence and SEM imaging techniques.
The final precipitation pattern and VEP deposition strongly depend on the interfacial transport processes, edge evaporation, and crystallization dynamics. A constant contact radius mode of evaporation with a mixture of capillary and Marangoni flows results in spatio-temporally varying edge deposits. Dendritic and cruciform-shaped crystals are majorly seen in all substrates except on steel, where regular cubical crystals are formed. The VEP deposition is higher near the threephase contact line and crystal surfaces. The results showed the role of interfacial processes in determining the initiation of fomite-type infection pathways in the context of COVID-19.
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Proteo-genomic analysis of SARS-CoV-2: A clinical landscape of SNPs, COVID-19 proteome and host responses
A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 and continues to be a global health challenge. To understand viral disease biology, a team of researchers at IISc carried out proteo-genomic analysis using next generation sequencing (NGS) and mass spectrometry on nasopharyngeal swabs of COVID-19 patients to examine clinical genome and proteome. The study confirms the mutability of SARS-CoV-2 showing multiple single nucleotide polymorphisms (SNPs). NGS analysis detected 27 mutations of which 14 are synonymous, 11 are missense and 2 are extragenic in nature. Phylogenetic analysis of SARS-CoV-2 isolates indicated their close relation to Bangladesh isolate and multiple origins of isolates within the country. The proteomic analysis, for the first time identified 13 different SARS-CoV-2 proteins from the clinical swabs. Of the total 41 peptides captured by HRMS, 8 matched to nucleocapsid protein, 2 to ORF9b, 1 to spike glycoprotein and ORF3a, with remaining peptides mapping to ORF1ab polyprotein. Additionally, host proteome analysis revealed several key host proteins to be uniquely expressed in COVID-19 patients. Pathway analysis of these proteins points towards modulation in immune response, especially involving neutrophil and IL-12-mediated signalling. Besides revealing the aspects of host-virus pathogenesis, the study opens new avenues to develop better diagnostic markers and therapeutic approaches
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Targeting inflammatory cytokine storm to fight against COVID-19-associated severe complications
COVID-19 is characterised by pneumonia progressing to breathing difficulty, acute respiratory distress syndrome (ARDS) and multi-organ failure. Clinical studies suggest excessive release of inflammatory mediators leading to cytokine storm, a phenomenon which appears to be potentially life-threatening in COVID-19. Across the globe, when the world authorities are grappling to contain the virus, a team of researchers from National Institute for Pharmaceutical Education and Research, Hyderabad presented a review on structure, pathophysiology of the virus that further sheds light on various clinical complications associated with the disease in order to open up/raise new horizons to explore various possible theoretical targets for COVID-19. The review also portrays a question and debates: Can targeting cytokine storm be a feasible approach to combat COVID-19?
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Inactivated COVID-19 vaccine BBV152/COVAXIN effectively neutralizes recently emerged B.1.1.7 variant of SARS-CoV-2
The rapid surge of SARS-CoV-2 cases due to the ‘variant of concern (VOC) 202 012/01’, also known as lineage B.1.1.7 or 20B/501Y.V1 in the UK, in December 2020, raised concerns in several countries due to its high transmissibility. Many of these countries had direct flights to and from the UK. Since the identification of the new variants of SARS-CoV-2 in the UK and South Africa, health experts have also expressed their concerns about their potential implications pertaining to vaccine efficacy. The root of such concerns was grounded in the structure of the SARS-CoV-2 variant, VOC-202012/01, which came to the centre stage of discussion due to its greater transmissibility in humans compared to the other known SARS-CoV-2 lineages.
This variant carries 17 mutations in the genome; 8 of which have been found in spike receptorbinding domain (RBD), mediating the attachment of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human cells. One of these mutations, N501Y, at position 501, has asparagine (N) replaced with tyrosine (Y) and has been identified to increase the binding affinity of SARS-CoV-2 to human and murine ACE2.2
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Neutralization of B.1.1.28 P2 variant with sera of natural SARS-CoV-2 infection and recipients of inactivated COVID-19 vaccine, Covaxin
The emergence of SARS-CoV-2 variants with mutations in the spike protein region lead to growing concerns about the efficacy of the currently available COVID-19 vaccines or neutralizing capability of the sera of individuals infected naturally with the earlier circulating strains. Although some of the vaccines seem to be effective against the UK variant, the efficacy of them against the South African variant has been demonstrated to be less. A SARS-CoV-2 vaccine that used an inactivation platform has been reported to be 50.7% efficacious from Brazil, where the B.126.96.36.199 variant is more prevalent (NCT0445659). Similarly, Brazil variant P2lineage (B.188.8.131.52) virus isolated from international travellers coming to India from abroad was used to determine the neutralization activity with sera of vaccine recipients and recovered COVID-19 cases.
n this study, it is determined the IgG immune response and neutralizing activity of the 19 convalescent sera specimens obtained from the recovered cases of COVID-19 and confirmed for B.1.1.7 (UK) (n=2), B.1.351 (South Africa) (n=2), B.184.108.40.206 (n=2), B1 lineage (n=13) (15-113 days post positive test). The data were compared with 42 participants immunized with an inactivated COVID-19 vaccine, Covaxin (BBV152), as part of phase II clinical trial (two months post the second dose). Neutralizing antibody (NAb) titers of all the serum specimens were evaluated against B.220.127.116.11 variant using plaque reduction neutralization test (PRNT50). Neutralization activity of B.18.104.22.168 was compared with prototype D614G variant as Covaxin vaccine has been developed using D614G variant
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Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra
As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being constantly used to investigate its transmissions and evolution. In the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in Maharashtra since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches was undertaken to identify possible new variants and gauge the fitness of current circulating strains. Phylogenetic analysis revealed that the predominant clade in circulation was a distinct newly identifiedlineage B.1.617 possessing common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein including within the receptor binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R and E484Q along with P681R in the furin cleavage site revealed that these may possibly result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility. The same two RBD mutations indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Experimental validation against a wider panel of mAbs, sera from vaccines and those that recovered from natural infection needs to be studied. The emergence of such local variants through the accumulation of convergent mutations during the COVID-19 second wave needs to be further investigated for their public health impact in the rest of the country and its possibility of becoming a VOC
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Prioritizing pregnant women for COVID-19 vaccination
Even though evidence for the safety and efficacy of COVID-19 vaccination in pregnancy is emerging, most countries currently do not offer COVID-19 vaccination to pregnant women, while a few leave the decision to the woman. Pregnant women are known to be at high risk of complications from COVID-19.
Vardhman Mahavir Medical College, Safdarjung Hospital, and NITI Aayog did a web search on policies for COVID-19 vaccination of pregnant women in two sets of countries – those bearing a high burden of COVID-19 cases globally and a second set with a high burden of maternal and under-five mortality. Of the top 20 COVID-19-affected countries, six countries allow and two have in place guidelines for preferential vaccination of pregnant women. In contrast, none of the high maternal and under-five mortality burden countries have such preferential vaccination guidelines in place. India and Indonesia with one-fifth of world’s population lie in both the groups, contributing 17% of COVID-19 cases, 11% of COVID-19 deaths, 17% of maternal, and 21% of under-five deaths globally, but do not allow COVID-19 vaccination of pregnant women. For COVID-19 not to further aggravate the already heavy existing burden of maternal and under-five mortality, there is a strong case for inclusion of pregnant women as a high priority group for COVID-19 vaccination. So, they recommend including COVID-19 vaccination in the routine protocol for antenatal care in all countries, particularly India and Indonesia, in view of their dual burden.
Virtual screening of curcumin and its analogs against spike surface glycoprotein of SARS-CoV-2 and SARS-CoV
COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel coronavirus SARS-CoV-2 and the 2002 SARS-CoV have 74% identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle.
The crystal structure of the SARS-CoV (6CRV: full length S protein) and SARS-CoV-2 Spike proteins (6M0J: Receptor binding domain, RBD) was used to determine potential small molecule inhibitors. Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties. In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby viral entry. The curcumin and its derivatives displayed binding energies, ?G, ranging from -10.98 to -5.12 kcal/mol (6CRV) and -10.01 to -5.33 kcal/mol (6M0J).
The least binding energy was seen in bis-demethoxycurcumin with ?G = -10.98 kcal/mol (6CRV) and -10.01 kcal/mol (6M0J). A good binding energy, drug likeness, and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors. However, further research is necessary to investigate the ability of these compounds as viral entry inhibitors.
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IISER Tirupati reviews “Global efforts on vaccines for COVID-19”
COVID-19 has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.
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Isolation and characterization of the new SARS-CoV-2 variant in travellers from the United Kingdom to India
Since its emergence in China during December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has marked its presence all across the globe. During this pandemic phase, the new genetic mutations acquired by the virus have led to new variants, indicating that the virus is evolving. This is indicated by the emergence of two SARS-CoV-2 variants, B.1.1.7 lineage (20B/501Y.V1 variant of concern [VOC] 202012/01) and B.1.351 lineage (20C/501Y.V2) identified from UK and South Africa, respectively. The B.1.1.7 lineage has eight mutations in Spike receptor-binding domain which mediates the attachment of the virus to the angiotensin-converting enzyme 2 receptor on the surface of human cells; whereas the B.1.351 lineage has the N501Y but not the 69/70 deletion. B.1.1.7 lineage phenotype has also attracted attention, as it proves to be much more transmissible among humans than the other known SARS-CoV-2 lineages. The genetic mutations in these new variants are associated with rapid transmission of the infection. However, its effect on the severity of the disease and vaccine efficacy has not yet studied.
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SARS-CoV-2 V501Y.V2 variant (B.1.351) detected in travellers from South Africa and Tanzania to India
The SARS-CoV-2 has been continuously mutating, leading to new variant strains since the emergence of the pandemic (2020-21). The first SARS-CoV-2 variant, 20I/501Y.V1 (B.1.1.7 Pangolin lineage) was reported from the United Kingdom (UK) which had 14 mutations and three amino acid deletions that influence the transmissibility of the virus in humans. Subsequently, emergence of new variants V501Y.V2 and 20J/501Y.V3 were also reported from South Africa and Brazil, respectively. Although, 50% increased transmissibility has been observed with V501Y.V2, the clinical severity associated with the variant is not known. The variant strains of SARS-CoV-2 have raised serious concerns related to their increased transmissibility and also their ability to evade the immune response elicited by available S genebased vaccines. The World Health Organization (WHO) has also reported a resurgence of SARS-CoV-2 infection in few countries due to the emergence of the variant strains.
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Clinical presentation of cases with SARS-CoV-2 reinfection/reactivation
The current COVID-19 pandemic is growing rapidly and healthcare workers (HCWs) are at a high risk of contagious SARS-CoV-2 infection. Frontline HCWs are at increased risk of COVID-19 as compared to the general population. With the passing time in the COVID-19 pandemic, the possibility of reinfection is an emerging threat. Although it is generally assumed that an episode of infection with SARS-CoV-2 would generate enough immune response providing protection for future infections, notwithstanding this, there are a few case reports demonstrating the possibility of re-infection. Like other coronaviruses, SARS-CoV-2 was expected to induce a monophasic disease with at least transient immunity. Nevertheless, rare cases of suspected COVID-19 “recurrence” or “reactivation” have been reported (REFS). Reinfection/reactivation of SARS-CoV-2 has been a matter of great interest from the immunological and vaccine perspective. However, little is known about the clinical presentation of such reinfection/reactivation.
A recombinant fragment of human surfactant protein-D binds spike protein and inhibits infectivity and replication of SARS-COV-2 in clinical samples
COVID-19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. The study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. The interaction of rfhSP-D with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR. In-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7; symptomatic, n=8; and negative controls n=15) demonstrated that treatment with 1.67 µM rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 µM). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 1.67 µM rfhSP-D. These results conclusively demonstrate that the calcium-independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.
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Postpartum psychosis in mothers with SARS-CoV-2 infection: A case series from India
The current COVID-19 pandemic is causing severe damage to the mankind through direct impact on health and also collaterally affecting all aspects of life including the mental health. The impending mental health crisis has attracted the attention of global experts and organisations necessitating the documentation of impact of COVID-19 on mental health, especially among the vulnerable populations. Pregnancy and the postpartum period are known to have increased vulnerability to psychiatric disorders. Earlier studies reported the association of other coronaviruses with a range of psychiatric disorders. However, there is no information on new-onset psychosis in asymptomatic patients or postpartum women with COVID-19. In the research, three cases of postpartum psychosis (PP) associated with asymptomatic COVID-19 managed at Topiwala National Medical College (TNMC) & B. Y. L. Nair Charitable Hospital (NH). NH is a an academic tertiary care public hospital and a dedicated COVID-19 hospital in Mumbai, receiving referrals from all over the Mumbai Metropolitan Region (MMR). In the initial phase of three months of COVID-19 pandemic (from 4 April 2020 to 31 July 2020), NH treated three asymptomatic, RT-PCR-confirmed COVID-19 women with PP. The demographic, clinical characteristics, delivery details and management of COVID-19 mothers with PP are described in the research paper.
Co-infection of malaria and dengue in pregnant women with SARS-CoV-2
Many low- and middle-income countries (LMICs) experience high rates of malaria and other neglected tropical diseases (NTDs), such as dengue. The COVID-19 pandemic complicates these matters further as COVID-19 in pregnant women is associated with an increased risk of preterm birth, and in some LMICs it is associated with a higher risk of maternal death. Furthermore, the clinical presentations of malaria and dengue strongly overlap with that of COVID-19, therefore posing an additional challenge for differential diagnosis. The PregCovid registry (https://pregcovid.com), registered with Clinical Trials Registry India (no. CTRI/2020/05/025423), is currently accumulating data from various regions in Maharashtra. The present study reports the clinical presentations, management, and outcomes of three pregnant women with COVID-19 who also had co-infection of malaria, and one with dengue, admitted to BYL Nair Hospital in Mumbai.
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Universal screening identifies asymptomatic carriers of SARSCoV-2 among pregnant women in India
Asymptomatic women with COVID-19 are at risk of infecting their newborns and also pose a risk to healthcare providers and other patients. Considering this, Indian Council of Medical Research (ICMR) recommended universal testing for SARS-CoV-2 in pregnant women. Maharashtra is the worst-hit state in India and universal screening strategy for pregnant women was implemented in several public hospitals during this time. In this study report of the outcome of implementation of this strategy is being provided.
Delirium in a pregnant woman with SARS-CoV-2 infection in India
In the current healthcare crisis due to COVID-19 pandemic, immediate dissemination of evidence is a priority for empowering the healthcare providers and policy makers. Currently, there is limited data on impact of COVID-19 on mental health of individuals residing in lowincome and middle-income countries (LMICs), especially pregnant women. Pregnant women are at increased risk of contracting COVID-19 and thus require special attention, especially while dealing with mental health issues. It is extremely challenging to manage mental health problems of pregnant women with COVID-19 in India and other LMICs due to inadequate health system infrastructure and lack of trained manpower and mental health services. Several challenges are being faced in the COVID-19 hospitals in LMICs, especially for the management of pregnant and postpartum women with COVID-19. In a dedicated COVID-19 facility, 885 pregnant women with COVID-19 were managed wherein more than 600 women delivered. In these women, increased anxiety and psychological distress related to COVID-19 was observed (unpublished data). Three cases of postpartum psychosis associated with COVID-19 were successfully managed at the COVID-19 hospital.
Persistence of SARS-CoV-2 in the first trimester placenta leading to vertical transmission and fetal demise from an asymptomatic mother
COVID-19 is caused by infection of the respiratory tract by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which survives in the tissues during the clinical course of infection but there is limited evidence on placental infection and vertical transmission of SARS-CoV-2. The impact of COVID-19 in first trimester pregnancy remains poorly understood. Moreover, how long SARS-CoV-2 can survive in placenta is unknown. In this report, a case of a pregnant woman in the first trimester who tested positive for SARS-CoV-2 at 8 weeks of gestation has been discussed, although her clinical course was asymptomatic.
At 13 weeks of gestation, her throat swab tested negative for SARS-CoV-2 but viral RNA was detected in the placenta, and the Spike (S) proteins (S1 and S2) were immunolocalized in cytotrophoblast and syncytiotrophoblast cells of the placental villi. Histologically, the villi were generally avascular with peri-villus fibrin deposition and in some areas the syncytiotrophoblast layer appeared lysed. The decidua also had fibrin deposition with extensive leukocyte infiltration suggestive of inflammation. The SARS-CoV-2 crossed the placental barrier, as the viral RNA was detected in the amniotic fluid and the S proteins were detected in the fetal membrane. Ultrasonography revealed extensively subcutaneous edema with pleural effusion suggestive of hydrops fetalis and the absence of cardiac activity indicated fetal demise. This is the first study to provide concrete evidence of persistent placental infection of SARS-CoV-2 and its congenital transmission is associated with hydrops fetalis and intrauterine fetal demise in early pregnancy.
Oral solution for ‘black fungus’ is now ready for technology transfer, says IIT Hyderabad Researchers
In 2019 Prof. Saptarshi Majumdar and Dr Chandra Shekhar Sharma from the Department of Chemical Engineering made a proven study about oral nanofibrous AMB to be effective for Kala Azar. This is a first-ever attempt to fabricate nanofibrous oral tablets of Amphotericin B for the potential cure of Leishmaniasis or Kala Azar. With two years of advancement of examination, the researchers are now confident that the technology can be transferred to suitable pharma partners for large-scale production. At present, the KalaAzar treatment is being used as a treatment for Black and other Fungus in the country, Because of its availability and affordability this oral drug must be allowed for emergency and immediate trial.
Due to its amphiphilic nature, the AmB has poor aqueous solubility and forms aggregates in the system, which stresses renal filtration and thus causing nephrotoxicity. This is the reason the oral administration has been abstained, although being the most comfortable and effective route. In present research funded by DST-Nanomission, a team led by Prof. Saptarshi Majumdar and Dr Chandra Shekhar Sharma along with their PhD scholars Mrunalini Gaydhane and Anindita Laha intended to deliver Amphotericin B orally at an extremely slow rate, of course within the therapeutic window. The purpose was to increase drug absorption and reduce aggregation, to lower the drug toxicity. For this, the team has selected gelatin, an FDA-approved polymer as an excipient for drug molecules.
Further, as gastrointestinal tract contains different enzymes which hydrolyze the polymers, the team has checked and confirmed the enzymatic stability of the tablet in pepsin. The significance of the nanofibrous tablets is depicted in the enclosed illustration. The main concern with high drug loading was if it imposes nephrotoxicity. To ensure this, the team has carried out a cell viability assay (MTT assay) against human kidney fibroblast cells which illustrated no evidence of cell toxicity caused by AmB as well as a minute amount of Glutaraldehyde crosslinker. The concept is also briefed in a video that can be watched at: https://youtu.be/LIIo5UCoYGY
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Website link: https://pcr.iith.ac.in/files/pressrelease/Oral%20solution%20for%20%E2%80%98black%20fungus%E2%80%99%20is%20now%20ready%20for%20technology%20transfer,%20says%20IIT%20Hyderabad%20Researchers.pdf
Psychological impacts of COVID-19 pandemic on the mode choice behaviour: A hybrid choice modelling approach
The COVID-19 pandemic is a pivotal moment in the history of mankind, which had a huge impact on the fast-paced world. The uncertainty associated with the plight of the pandemic, pushed the world towards a sense of insecurity and panic. Apart from the disease, the psychological problem connected to the lockdowns has caused an unprecedented change in the thought process of people towards travel.
A recent study conducted by two researchers at the IIT Ropar aimed to statistically illustrate the change the pandemic and lockdowns brought upon the travel mode choice behaviour. An Integrated choice and latent variable (ICLV) framework was adapted to understand the impact of the novel behavioural constructs, such as awareness of the disease and people’s perception of the strictness of lockdown towards the mode choice in the post-pandemic scenario. Different trip types were characterized according to the nature of the trip, and their mode choice were assessed separately for the impact of the latent constructs. The results suggest that the awareness of the disease and the perception of strictness of the lockdown implemented play a major role in affecting the change of the mode choice of people. Further, the perception of safety in public transport, characterized by the social distancing and sanitization measures, determine the willingness of people towards the choice of public transit systems. The study concludes with a focus on the policies, which could be implemented for a safe travel in the post lockdown stage.
Novel Coronavirus 2019 (2019-nCoV) Infection: Preparedness and Management in Resource-limited Settings of PICU
The 2019-novel coronavirus predominantly affects the respiratory system with manifestations ranging from upper respiratory symptoms to full blown acute respiratory distress syndrome (ARDS).
The coronavirus disease mainly starts with a respiratory illness and about 5-16% requires intensive care management for ARDS and multi-organ dysfunction. Children account for about 1-2% of the total cases, and 6% of these fall under severe or critical category requiring Pediatric Intensive Care Unit (PICU) care. A study has been conducted by a team of researchers in this regard.
Use of high flow devices and non-invasive ventilation has been discouraged due to high chances of aerosol generation. Early intubation and mechanical ventilation are essential to prevent complications and worsening, especially in resource-limited settings, with very few centres having expertise to manage critical cases.
Hydrophobic viral filter in the ventilator circuit minimizes chances of transmission of the virus. Strategies to manage ARDS in COVID-19 include low tidal volume ventilation with liberal sedation-analgesia. At the same time, prevention of transmission of the virus to healthcare workers is extremely important in the intensive care setting dealing with severe cases and requiring procedures generating aerosol. PGIMER provide guidance on non-invasive respiratory support, intubation and management of ARDS in a child with COVID-19.
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Research paper on heat-stable vaccine for COVID-19
Many of the COVID-19 vaccines need cold temperatures during their transportation. Exposure to higher temperatures may lose the potency of these vaccines. Researchers from the Indian Institute of Science Bangalore and other collaborators from IISER Thiruvananthapuram, THSTI Faridabad, and the IISc-incubated start-up Mynvax have developed a heat-stable vaccine candidate for COVID-19. The so called ‘warm vaccine’ would not require cold chain transportation which is extremely important in the Indian context where the vaccine can be delivered to towns and villages without the requirement of cold temperatures for transportation. The research has been accepted for publication in the Journal of Biological Chemistry, a peer-reviewed scientific journal published by the American Society for Biochemistry and Molecular Biology
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Global air quality and COVID-19 pandemic: Do we breathe cleaner air?
The global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has challenged most countries worldwide. It was quickly recognized that reduced activities (lockdowns) during the COVID-19 pandemic produced major changes in air quality. Research objective was to assess the impacts of COVID-19 lockdowns on ground-level PM 2.5, NO2 , and O3 concentrations on a global scale. Data was obtained from 34 countries, 141 cities, and 458 air monitoring stations on 5 continents (few data from Africa). On a global average basis, a 34.0% reduction in NO2 concentration and a 15.0% reduction in PM 2.5 were estimated during the strict lockdown period (until April 30, 2020). Globally, average O3 concentration increased by 86.0% during this same period. Individual country- and continent-wise comparisons have been made between lockdown and business-as-usual periods. Universally, NO2 was the pollutant most affected by the COVID-19 pandemic. These effects were likely because its emissions were from sources that were typically restricted (i.e., surface traffic and non-essential industries) by the lockdowns and its short lifetime in the atmosphere. These results indicate that lockdown measures and resulting reduced emissions reduced exposure to most harmful pollutants and could provide global-scale health benefits. However, the increased O3 may have substantially reduced those benefits, and more detailed health assessments are required to accurately quantify the health gains. At the same time, these restrictions were obtained at substantial economic costs and with other health issues (depression, suicide, spousal abuse, drug overdoses, etc.). Thus, any similar reductions in air pollution would need to be obtained without these extensive economic and other consequences produced by the imposed activity reductions.
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Binding insight of clinically oriented drug Famotidine with the identified potential target of SARS-CoV-2
The coronavirus pandemic (COVID-19) has been associated with acute respiratory distress syndrome resulted from an enveloped, positive-sense, single-stranded RNA beta-coronavirus that has a genome of over 29 kb in length (Prajapat et al., 2020; Sarma et al., 2020). Six members of the Coronaviridae family were previously known to infect humans, including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), in 2002 and 2012, respectively. SARS-CoV-2 is the latest addition to the family and has less severe symptoms and a lower mortality rate (6.4%), but more infectious (Zhu et al., 2020; Muralidharan et al., 2020; Gupta et al., 2020) than the SARS-CoV and MERS-CoV with the fatality rate of 10% and 36%, respectively (Chang et al., 2006). An increasing number of infections and the death toll despite concerted efforts to contain the pandemic using various strategies usher an adverse global impact on health and economics (Petropoulos & Makridakis, 2020), impelling to discover preventive therapeutics as quickly as possible (Cao et al., 2020). The scenario is further made worst by the fact that at present, no clinically effective drug has been approved for the treatment of this virus infection.
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Adhatoda Vasica attenuates inflammatory and hypoxic responses in preclinical mouse models: Potential for repurposing in COVID-19- like conditions
COVID-19 pneumonia has been associated with severe acute hypoxia, sepsis-like states, thrombosis and chronic sequelae including persisting hypoxia and fibrosis. The molecular hypoxia response pathway has been associated with such pathologies and a recent observations on anti-hypoxic and anti-inflammatory effects of whole aqueous extract of Adhatoda Vasica (AV) prompted the researchers to explore its effects on relevant preclinical mouse models. In this study, they tested the effect of whole aqueous extract of AV in murine models of bleomycin-induced pulmonary fibrosis, Cecum Ligation and Puncture (CLP)-induced sepsis, and siRNA-induced hypoxia-thrombosis phenotype. The effect on lung of AV-treated naïve mice was also studied at transcriptome level and also determined if the extract may have any direct effect on SARS-CoV-2 replication. Oral administration AV extract attenuates increased airway inflammation, levels of transforming growth factor-b1 (TGF-b1), IL-6, HIF-1a and improves the overall survival rates of mice in the models of pulmonary fibrosis and sepsis and rescues the siRNA-induced inflammation and associated blood coagulation phenotypes in mice and also observed downregulation of hypoxia, inflammation, TGF-b1, and angiogenesis genes and upregulation of adaptive immunity-related genes in the lung transcriptome. AV treatment also reduced the viral load in Vero cells infected with SARS-CoV-2
Cancer vs. SARS-CoV-2-induced inflammation: Study suggests overlapping functions and pharmacological targeting
Inflammation is an intrinsic defence mechanism triggered by the immune system against infection or injury. Chronic inflammation allows the host to recover or adapt through cellular and humoral responses, whereas acute inflammation leads to cytokine storms resulting in tissue damage. In a review, the researchers presented the overlapping outcomes of cancer inflammation with virus-induced inflammation. The study emphasises how anti-inflammatory drugs that work against cancer inflammation may work against the inflammation caused by the viral infection. It is established that the cytokine storm induced in response to SARS-CoV-2 infection contributes to disease-associated mortality. While cancer remains the second among the diseases associated with mortality worldwide, cancer patients' mortality rates are often observed upon extended periods after illness, usually ranging from months to years. However, the mortality rates associated with COVID-19 disease are robust. The cytokine storm induced by SARS-CoV-2 infection appeared to be responsible for the multi-organ failure and increased mortality rates. Since both cancer and COVID-19 disease share overlapping inflammatory mechanisms, repurposing some anticancer and anti-inflammatory drugs for COVID-19 may lower mortality rates. Here, they review some of these inflammatory mechanisms and propose some potential chemotherapeutic agents to intervene in them and also discuss the repercussions of anti-inflammatory drugs such as glucocorticoids and hydroxychloroquine with zinc or antiviral drugs such as ivermectin and remdesivir against SARS-CoV-2-induced cytokine storm. In this review, the researchers emphasise on various possibilities to reduce SARS-CoV-2-induced cytokine storm.
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HARIOM, an optical detection method for COVID-19
In order to define public health policies, simple, inexpensive, and robust detection methods for SARS-CoV-2 are vital for mass-testing in resource-limited settings. The current choice of molecular methods for identification of SARS-CoV-2 infection includes nucleic acid-based testing (NAT) for viral genetic material and antigen-based testing for viral protein identification. Host exposure is detected using antibody detection assays. While NATs require sophisticated instrument and trained manpower, antigen tests are plagued by their low sensitivity and specificity. Thus, a test offering sensitive detection for presence of infection as a colorimetric readout holds promise to enable mass testing in resource-constrained environments by minimally trained personnel. The novel HRPZyme Assisted Recognition of Infection by Optical Measurement (HARIOM) assay combines specificity of NATs with sensitivity of enzymatic assays resulting in enhanced signal-to-noise ratios in an easily interpretable colorimetric readout. Using this assay, the researchers could detect up to 102 copies of synthetic viral RNA spiked in saliva as a detection matrix. Validating their assay on suspected human subjects, they found concordance with PCRbased readouts with visible colorimetric distinction between positive and negative samples in less than an hour. This assay holds the potential to aid in mass screening to detect SARS-CoV-2 infection by facilitating colorimetric detection with minimal resources and trained personnel.
Computational analysis and phylogenetic clustering of SARS-CoV-2 genomes
Following the rapid human-to-human transmission of the infection, institutes around the world have made efforts to generate genome sequence data for the virus. With thousands of genome sequences for SARS-CoV-2 now available in the public domain, it is possible to analyze the sequences and gain a deeper understanding of the disease, its origin, and its epidemiology. Phylogenetic analysis is a potentially powerful tool for tracking the transmission pattern of the virus with a view to aiding identification of potential interventions. Toward this goal, a comprehensive protocol has been created for the analysis and phylogenetic clustering of SARSCoV-2 genomes using Nextstrain, a powerful open-source tool for the real-time interactive visualization of genome sequencing data. Approaches to focus the phylogenetic clustering analysis on a particular region of interest are detailed in this protocol.
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After FELUDA, CSIR develops paper test RAY to identify COVID-19 virus variants within an hour
The Council of Scientific & Industrial Research (CSIR) has developed a new COVID-19 test that can identify the variant of the virus identified in the United Kingdom within an hour. The new test is called RAY (Rapid variant AssaY), in an homage to legendary Bengali filmmaker and author Satyajit VIGYAN PRASAR 60 Ray. It has been created by the same CSIR team that in April last year designed ‘FELUDA’, a paperbased COVID-19 test named after the fictional detective that Ray had created. The RAY test has been developed at a time when countries across the world are actively scrutinising international travellers for new variants of the COVID-19 virus, such as the variant identified in the UK, which spreads faster than the original SARS-CoV-2 variant.
Studies on immunological, nutritional and comorbidity factors impacting response to infection and vaccination – an initiative funded by Office of the PSA
Since the beginning of the COVID-19 pandemic, Pune has been one of the worst hit cities in the world. The total number of Coronavirus-positive patients to date (as on 9 May 2021) has reached 4,46,564 out of which 4,05,474 have been cured while 7358 have died. There are still 33,732 active patients undergoing treatment in various hospitals. Pune has, thus, been hit incredibly hard by the pandemic. During the beginning of the pandemic, Pune city, managed by Pune Municipal Corporation (PMC), successfully initiated and maintained Government mandated data compilation from clinic and hospital-level data at the city level. The PMC and Pune Knowledge Cluster (PKC) entered into a collaborative agreement in April 2020 to develop and implement local policies based on the analysis of the COVID-19 patient-level data. The major activities of this collaboration included curation of the data, analysis of data at sub-region level called Prabhags, modelling of the data to project the pandemic curve, constitution of a project to assess the prevalence of positive serology among the population and coordination for resource procurements and allocation. The PKC (www.pkc.org.in) is funded by the cluster initiative of the office of the Principal Scientific Adviser to the Government of India. The studies outlined here, however, can easily be scaled up across various regions of the country, which will generate public health data of enormous value for immediate policy decisions to address the current pandemic and also for the future. Differences in the scale of the infection spread and severity of the clinical outcomes of infection highlight the importance of framing polices and strategies to fight the pandemic, both in the short-term and the long-term, based on ground level data and scientific investigations of the infectivity of the virus and immune response of infected people. Detailed studies on both the viral pathogen and host factors are key to understand and control the pandemic, prevent loss of lives, and reduce long-term health impact. Viral genome sequencing as the infection spreads across diverse human populations and as they are vaccinated and immunotyping of populations based on immune response to infection and vaccination need to be taken up immediately on war-footing. In addition, factors such as nutritional diversity among the populations and other comorbidities that impact the risks of severe disease need to be studied in more detail. Such studies have minimal epidemiological and public health value unless they are designed based on ground level granular data on the pandemic since its beginning.
Genomic surveillance of SARS-CoV-2 using wastewater in Bengaluru city – an initiative supported by Office of PSA
Bangalore Water Supply and Sewerage Board (BWSSB) manages wastewater systems through more than 25 Sewage Treatment Plants (STPs) and supplies treated water for irrigation, industrial use, and recharging of urban lakes (https://www.bwssb.gov.in). National Centre for Biological Sciences (NCBS) is currently engaging with BWSSB for a regular sampling of non-treated, treated, and sludge samples from different STPs. These samples are to be tested for SARSCoV-2 RNAs using standard qRT-PCR and also to be used for standardizing and optimizing other novel methods. A formal Memorandum of Understanding is in place between NCBS and BWSSB to perform the abovementioned activities. Wastewater epidemiology is a powerful tool to understand the dynamics of not just SARS CoV2 but many other emerging pathogens. In addition to detecting the SARS-CoV-2 genome, this study would identify variants circulating in the populations. The repeated sampling at regular intervals would help track emerging variants and their dynamics over time. This information can be correlated with the clinical data from the catchment area. Besides, prevalence information would actively be used as an indicator of infection load and the health status of the catchment area population. By actively engaging with BWSSB, NCBS hopes to build capacity at BWSSB to implement wastewater epidemiology for public health purposes. This collaborative effort would strengthen the knowledge on the impact of COVID-19 in the city and build the capabilities of both institutions - BWSSB and NCBS- to understand and manage wastewater in Bengaluru city better.
Rapid response in a pandemic through genomic surveillance of SARS-CoV-2 genomes – an initiative supported by Office of PSA
SARS-CoV-2 is the coronavirus that causes COVID-19, a pandemic that has gripped the entire world since November 2019. Several countries throughout the world have been through waves and troughs of infection. Through these difficult times, science-based response remains at the forefront of what we can do. The aim is to work at this science-based pandemic response interface. Genomic surveillance of the virus as it evolves and changes are critical for vaccine calibration due to the generation of variants. Such surveillance remains poor in India, despite interest and some level VIGYAN PRASAR 62 of national investment in such an endeavour. This is particularly true in the context of vaccination. While vaccine breakthrough is now recognized as most significant, the genomic characteristics of the viras that allows it to breakthrough depend on adequate genomic surveillance. The proposal address the genomics and immunology of vaccine breakthrough, correlated with disease severity in multiple geographies in India -- Vellore in Tamil Nadu and Bengaluru in Karnataka -- by creating and building on existing infrastructure and cohorts set up during this on-going pandemic. This will be coordinated and executed by some of the best hospitals (CMC, Vellore; Baptist Hospital and St Johns Research institute) and most accomplished institutes like DBT’s inStem and TIFR-NCBS in the country.
A pan-national effort on enhanced viral surveillance to better track COVID-19 and vaccinations in India: The second wave and beyond – an initiative supported by Office of PSA
Pathogens like viruses have short generation times and high reproductive rates. This allows them to evolve or change very rapidly. SARS-CoV-2, the virus responsible for the on-going pandemic of COVID-19, mutates and changes continuously as it transmits from person to person. While most new mutations or changes are of little to no consequence, others are able to transmit better, escape existing immunity, dodge detection by diagnostic kits, or have serious clinical impacts. Continuous and on-going genome sequencing of the virus and genomic surveillance help better understand how SARS-CoV-2 is evolving. Such sequencing will eventually allow us to mitigate the risks posed by the ever-changing genomic landscape of the virus, particularly making course correction to vaccination strategies. Furthermore, genomics coupled with host serum analyses can help to explain why people respond to COVID-19 in different ways, therefore helping to identify and better protect those at greater risk of severe disease. Genomic surveillance for both retrospective and prospective (future infections), when coupled with clinical data, allow us to infer correlations between viral mutations and patient outcomes. All centres will work with their respective states and clinical partners, who have access to epidemiological clinical data on disease outcomes. Such analyses will allow understanding the role of virus evolution in disease burden. Patient genomics can help identify individual-specific responses and correlates.
From a practical perspective, the only way forward is vaccination. Vaccine breakthrough, when vaccinated people get infected, is now recognized as significant. The genomic characteristics of the virus that allow it to breakthrough also require adequate genomic surveillance.
1. Retrospective genomic surveillance: Genome sequencing of archived samples representing dynamics of the pandemic (high vs. low incidence zones; asymptomatic/mild vs. severe symptoms/mortality; paediatric/young age vs. old age infections etc.).
2. Prospective genomic surveillance: Genome sequencing to i) track variant emergence and transmission using sampling strategies defined by sociodemographics; ii) reconstruct epidemiologic history using both phylogenetic analysis and gene genealogy; iii) characterize and draw inferences from clinical phenotypes including vaccine breakthroughs, reinfections, and others; and iv) conduct environmental surveillance (of sewage and waste water), potential to complement human surveillance and support of early interventions (considering large proportion of infected people are asymptomatic).
3. Build human resource: Bioinformatics and genomic epidemiology training for pathogen genomics across institutions and platforms. Adopt evolving technology for sequencing, VIGYAN PRASAR 63 analyses and rapid identification of viral variants, build workflows, use of pipelines, quality checks, data validation and approaches to rapid/real-time data sharing.
4. Applied science: Use of sequencing data to inform and support evaluations relevant to public health, vaccines, drug development and clinical prediction.
Partners, such as Pune Knowledge Cluster (coordinator representing CSIR-NCL, IISER Pune, SPPU, NCCS, BJMC, AFMC, KEM and Symbiosis Hospitals), CCMB, NCBS, InStem, St. Johns hospital, Baptist Hospital, NIMHANS, Bangalore Water Supply and Sewage Board, and CMC Vellore are among those whose objectives of success include the well-being and health of the greater populace.
Full-genome sequences of the first two SARS-CoV-2 viruses from India by ICMR-NIV, Pune
SARS-CoV-2 has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.
A review vaccines and therapies in development for SARS-CoV-2 infections
The current COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. The virus causes severe respiratory symptoms which manifest disproportionately in the elderly. Given the current severity of the outbreak, there is a great need for antiviral therapies and vaccines to treat and prevent COVID-19. Given the current lack of treatments for SARS-CoV-2, there is a great demand to produce and scale therapeutics and vaccines to combat COVID-19. Before the current outbreak, there was not even a standardized treatment for the original SARS-CoV infections. Research and development are critically needed to protect against SARS-CoV-2 and future coronaviruses infections. In a review, researchers from ICMR-National Institute of Virology (NIV) and other international institutes have discussed the epidemiology and structure of the novel coronavirus. They also discussed two promising vaccine and three therapeutic treatments in development along with two experimental therapies that should be further investigated. If these treatments can be successfully developed and scaled, the length and severity of the COVID-19 outbreak could potentially be attenuated. Until then, social distancing and maintaining effective sanitization remain good tools for the public.
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Research contributions through publications by ICMR-NIV on COVID-19
National Institute of Virology (ICMR-NIV) printed research publications on COVID-19 to reach out to the people. These publications had details about effects of Coronavirus and COVID-19 on the human body. There are forty publication/research papers that were published during the pandemic which focuses on the following:
1) Genetic characterization of SARS-CoV-2 & implications for epidemiology, diagnostics & vaccines in India.
2) PLACID Trial Collaborators. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)
3) Guidance for building a dedicated health facility to contain the spread of the 2019 novel coronavirus outbreak.
4) Evaluation of RdRp & ORF-1b-nsp14-based real-time RT-PCR assays for confirmation of SARS-CoV-2 infection: An observational study.
5) Utility of a modified heat inactivation method for direct detection of SARS-CoV-2 by RTqPCR in viral transport medium bypassing RNA extraction: A preliminary study.
6) Performance evaluation of Truenat Beta CoV & Truenat SARS-CoV-2 point-of-care assays for coronavirus disease 2019.
7) Lessons learnt during the first 100 days of COVID-19 pandemic in India.
8) The enigmatic COVID-19 pandemic.
9) Time to revisit national response to pandemics.
10) Perspectives for repurposing drugs for the coronavirus disease 2019.
11) Development of in vitro transcribed RNA as positive control for laboratory diagnosis of SARS-CoV-2 in India.
12) Neutralizing antibody responses to SARS-CoV-2 in COVID-19 patients.
13) Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial.
14) Laboratory preparedness for SARS-CoV-2 testing in India: Harnessing a network of Virus Research & Diagnostic Laboratories.
15) Laboratory surveillance for SARS-CoV-2 in India: Performance of testing & descriptive epidemiology of detected COVID-19
16) Identification of SARS-CoV-2 clusters from symptomatic cases in India.
17) Inactivation of SARS-CoV-2 by gamma irradiation.
18) How artificial intelligence may help the Covid-19 pandemic: Pitfalls and lessons for the future.
19) Evaluation of the susceptibility of mice & hamsters to SARS-CoV-2 infection.
20) Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS-CoV-2 vaccine candidates in the Syrian hamster model.
21) Biorisk assessment for infrastructure & biosafety requirements for the laboratories providing coronavirus SARS-CoV-2/(COVID-19) diagnosis.
22) Comparison of the immunogenicity & protective efficacy of various SARS-CoV-2 vaccine candidates in non-human primates. VIGYAN PRASAR 66
23) SARS-CoV-2 & influenza A virus co-infection in an elderly patient with pneumonia.
24) Prevalence of SARS-CoV-2 infection in India: Findings from the national serosurvey.
25) Transcriptome & viral growth analysis of SARS-CoV-2-infected Vero CCL-81 cells.
26) Natural Selection Plays an Important Role in Shaping the Codon Usage of Structural Genes of the Viruses Belonging to the Coronaviridae Family.
27) Quasispecies analysis of the SARS-CoV-2 from representative clinical samples: A preliminary analysis.
28) Prediction of potential small interfering RNA molecules for silencing of the spike gene of SARS-CoV-2.
29) Steps, implementation and importance of quality management in diagnostic laboratories with special emphasis on coronavirus disease-2019.
30) Genomic analysis of SARS-CoV-2 strains among Indians returning from Italy, Iran & China, & Italian tourists in India.
31) Respiratory virus detection among the overseas returnees during the early phase of COVID-19 pandemic in India.
32) Pooled testing for COVID-19 diagnosis by real-time RT-PCR: A multi-site comparative evaluation of 5- & 10-sample pooling.
33) Transmission electron microscopy imaging of SARS-CoV-2.
34) Development of indigenous IgG ELISA for the detection of anti-SARS-CoV-2 IgG.
35) First isolation of SARS-CoV-2 from clinical samples in India.
36) SARS-CoV-2 detection in sewage samples: Standardization of method & preliminary observations.
37) Vaccines and Therapies in Development for SARS-CoV-2 Infections.
38) Isolation and characterization of VUI-202012/01, a SARS-CoV-2 variant in travellers from the United Kingdom to India.
39) Full-genome sequences of the first two SARS-CoV-2 viruses from India.
40) Detection of coronaviruses in Pteropus & Rousettus species of bats from different States of India.
SARS-CoV-2: Phylogenetic origins, pathogenesis, modes of transmission, and the potential role of nanotechnology
The COVID-19 pandemic has elicited a rapid response from the scientific community with significant advances in understanding the causative pathogen (SARS-CoV-2). Mechanisms of viral transmission and pathogenesis as well as the structural and genomic details have been reported, which are essential in guiding containment, treatment, and vaccine development efforts. The present paper is a concise review of the recent research in these domains and an exhaustive analysis of the genomic origins of SARS-CoV-2. Particular emphasis has been placed on the pathology and disease progression of COVID-19 as documented by recent clinical studies, in addition to the characteristic immune responses involved therein. Furthermore, the potential of nanomaterial and nanotechnology to develop diagnostic tools, drug delivery systems, and personal protective equipment design within the on-going pandemic context have also been VIGYAN PRASAR 67 discussed and the paper is going to be a ready resource for researchers to gain succinct, up-todate insights on SARS-CoV-2.
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IISER Bhopal’s research shows coronavirus ‘N protein’ plays critical role in viral transmission
Researchers from the Indian Institute of Science Education and Research (IISER), Bhopal have shown that proteins from the COVID-19 virus other than the well-known ‘spike protein’ can play a critical role in the infectivity of the virus. The establishment of SARS CoV-2 spike-pseudotyped lentiviral (LV) systems have enabled the rapid identification of entry inhibitors and neutralizing agents, alongside allowing for the study of this emerging pathogen in BSL-2 level facilities. While such frameworks recapitulate the cellular entry process in ACE2+ cells, they are largely unable to factor in supplemental contributions by other SARS-CoV-2 genes. To address this, researchers from IISER, Bhopal performed an unbiased open reading frame (ORF) screen and identified the nucleoprotein (N) as a potent enhancer of spikepseudotyped LV particle infectivity and further demonstrate that this augmentation by N renders LV spike particles less vulnerable to the neutralizing effects of a human IgG-Fc-fused ACE2 microbody. Biochemical analysis revealed that the spike protein is better enriched in virions when the particles are produced in the presence of SARS-CoV-2 nucleoprotein. Importantly, this improvement in infectivity is achieved without a concomitant increase in sensitivity towards RBD bindingbased neutralization. The results hold important implications for the design and interpretation of similar LV pseudotyping-based studies.
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Protective roles of flu infections and BCG vaccination in lowering COVID-19 mortality
The recent COVID-19 pandemic has caused a great loss of lives as well as affected economies in several countries. The loss of COVID-19 deaths is far greater in some countries compared to others. This observation led to perform epidemiological analysis using disease and vaccination data in the public domain with respect to measles, hepatitis B virus, polio, tuberculosis, and flu from twenty five countries across the globe. There is no correlation between COVID-19 incidences or deaths as well as vaccination coverage with respect to diseases such as measles, hepatitis B virus, and polio. However, countries with lower cases of tuberculosis and higher cases of flu have a significant correlation with respect to COVID-19 deaths. In fact, countries with high BCG vaccination coverage show a significant negative correlation with COVID-19 deaths. Surprisingly, countries such as the USA, Italy, France and Spain which have flu vaccination, but not BCG vaccination, show maximum number of COVID-19 deaths. It appears that high numbers of flu infections are protective and can decrease the number of COVID-19 deaths. Importantly, countries with high flu cases and BCG vaccination, such as India, Egypt, South Africa etc., show relatively lower COVID-19 deaths, reinforcing the protective roles of BCG vaccination. Notably, these general trends are statistically significant for COVID-19 deaths but not COVID-19 incidences. The implications of results are discussed with respect to the roles of microbial infections in the respiratory tract, vaccinations, and other factors in lowering COVID-19 deaths.
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Mechanistic modelling of the SARS-CoV-2 and immune system interplay unravels design principles for diverse clinico-pathological outcomes
The disease caused by SARS-CoV-2 is a global pandemic that threatens to bring long-term changes worldwide. Approximately 80% of the infected patients are asymptomatic or have mild symptoms such as fever or cough, while rest of the patients have varying degrees of severity of symptoms, with 3-4% mortality rate. Severe symptoms such as pneumonia and Acute Respiratory Distress Syndrome can be caused by tissue damage mostly due to aggravated and unresolved innate and adaptive immune response, often resulting from a cytokine storm. However, the mechanistic underpinnings of such responses remain elusive, with an incomplete understanding of how an intricate interplay among infected cells and cells of innate and adaptive immune system can lead to such diverse clinico-pathological outcomes.
A dynamical systems approach to dissect the emergent nonlinear intra-host dynamics among virally infected cells, the immune response to it, and the consequent immunopathology. By mechanistic analysis of cell-cell interactions, key parameters affecting the diverse clinical phenotypes associated with COVID-19 have been identified. This minimalistic yet rigorous model can explain the various phenotypes observed across the clinical spectrum of COVID-19, various co-morbidity risk factors such as age and obesity, and the effect of antiviral drugs on different phenotypes. It also reveals how a fine-tuned balance of infected cell killing and resolution of inflammation can lead to infection clearance, while disruptions can drive different severe VIGYAN PRASAR 69 phenotypes. These results will help further the case of rational selection of drug combinations that can effectively balance viral clearance and minimize tissue damage simultaneously.
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Genomics of Indian SARS-CoV-2: Implications in genetic diversity, possible origin and spread of virus by IISc team
I study has been conducted by the researchers at the Indian Institute of Science, Bangalore that aims to determine the genetic diversity among Indian SARS-CoV-2 viral isolates in comparison to the strains that are occurring worldwide. In addition to identification of types of viral strains in India, it is anticipated that the study will help in understanding the source of virus origin, route of spread, transmission dynamics of the virus, disease severity, possible viral strains for vaccine development, right type of diagnostic kits, and possibly developing relaxation models of social distancing.As on 7 June 2020, IISc team has completed analysis of 687 Indian viral genomes and found several interesting findings. The potential origin to be countries mainly from Oceania, Europe, Middle East and South Asia regions, which strongly imply the spread of virus through most travelled countries. Among different clades of the virus as identified by Global Initiative on Sharing All Influenza Data (https://www.gisaid.org/), Indian SARS-CoV-2 viruses are enriched with certain types more than others. Analysis of the Indian SARS-CoV-2 genomes will continue as more sequences are available. The team will start sequencing of SARS-CoV-2 viruses made available and look forward to finding India-specific genetic variation. The team will also monitor the dynamics of different viral strains over time in India. Efforts are also in progress to find the functional impact of high occurrence non-synonymous mutations on the viral protein functions and use this information towards understanding immune escape mechanism and also developing mutant specific therapies.
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Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARS-CoV-2 infection
The entry of SARS-CoV-2 into target cells requires the activation of its surface spike protein, S, by host proteases. The host serine protease TMPRSS2 and cysteine proteases Cathepsin B/L can activate S, making two independent entry pathways accessible to SARS-CoV-2. Blocking the proteases prevents SARS-CoV-2 entry in vitro. This blockade may be achieved in vivo through ‘repurposing’ existing drugs and offers a potential treatment option for COVID-19, currently in clinical trials. The researchers at Indian Institute of Science, Bangalore found that surprisingly drugs targeting the two pathways, although independent, could display strong synergy in blocking virus entry. They predicted this synergy first using a mathematical model of SARS-CoV-2 entry and dynamics in vitro. The model considered the two pathways explicitly, let the entry efficiency through a pathway depend on the corresponding protease expression level, which varied across cells, and let inhibitors compromise the efficiency in a dose-dependent manner. Analysing their model, the researchers showed that the synergy was novel and arose from effects of the drugs at both the single cell and the cell population levels. Validating our predictions, they found that available in vitro data on SARS-CoV-2 and SARS CoV entry displayed this synergy. Exploiting the synergy may improve the deployability of drug combinations targeting host proteases required for SARS-CoV-2 entry.
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