In silico evaluation of potential inhibitory activity of remdesivir, favipiravir, ribavirin and galidesivir active forms on SARS-CoV-2 RNA polymerase

Celik, Ismail; Erol, Meryem; Duzgun, Zekeriya

Since the outbreak emerged in November 2019, no effective drug has yet been found against SARS-CoV-2. Repositioning studies of existing drug molecules or candidates are gaining in overcoming COVID-19. Antiviral drugs such as remdesivir, favipiravir, ribavirin, and galidesivir act by inhibiting the vital RNA polymerase of SARS-CoV-2. The importance of in silico studies in repurposing drug research is gradually increasing during the COVID-19 process. The present study found that especially ribavirin triphosphate and galidesivir triphosphate active metabolites had a higher affinity for SARS-CoV-2 RNA polymerase than ATP by molecular docking. With the Molecular Dynamics simulation, we have observed that these compounds increase the complex's stability and validate the molecular docking results. We also explained that the interaction of RNA polymerase inhibitors with Mg(++), which is in the structure of NSP12, is essential and necessary to interact with the RNA strand. In vitro and clinical studies on these two molecules need to be increased. [Image: see text]