Executive Summary : | Nucleoside/tide modification is a crucial area in synthetic biology and drug discovery, with modified nucleosides being used as therapeutics and biological probes against various life-threatening diseases, including viral infections. Nucleoside analogues target viral nucleic acid replication, which is crucial in regulating viral replication. However, misincorporation or mismatch of nucleotides can cause dysfunction of viral RdRps. Nucleoside-analogues exploit this misincorporation mechanism to control viral replication. The emergence of resistance against current antiviral therapeutics is a concern, and the development of newer antiviral RdRp inhibitors with improved pharmacological profiles is urgently needed. A new class of nucleoside analogues, such as carboline nucleosides, could be a compelling alternative to current antiviral nucleosides. Carboline is the basic scaffold in several drugs and natural products, and carboline heterocycles contain pyridine and indole moiety nucleobases. A novel synthetic route has been developed to construct carboline nucleosides, which have been docked against SARS-CoV-2 RdRp and shown promising results compared to Favipiravir. The researchers plan to extend the scope of the nucleosides by validating efficacy against SARS-CoV-2 RdRp and test the molecules against other RNA viruses, such as dengue virus, to develop broad-spectrum antivirals against RNA viruses. |