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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.
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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.188.8.131.52 variant is more prevalent (NCT0445659). Similarly, Brazil variant P2lineage (B.184.108.40.206) 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.220.127.116.11 (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.18.104.22.168 variant using plaque reduction neutralization test (PRNT50). Neutralization activity of B.22.214.171.124 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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