Modeling the Binding Mechanism of Remdesivir, Favilavir, and Ribavirin to SARS-CoV-2 RNA-Dependent RNA Polymerase.

ABSTRACT: Recent efforts to repurpose drugs to combat COVID-19 have identified Remdesivir as a candidate. It acts on the RNA-dependent, RNA polymerase (RdRp) of the SARS-CoV-2 virus, a protein complex responsible for mediating replication of the virus's genome. However, its exact action mechanism, and that of other nucleotide analogue inhibitors, is not known. In this study, we examine at the molecular level the interaction of this drug and that of similar nucleotide analogue inhibitors, ribavirin and favilavir, by relying on atomistic molecular simulations and advanced sampling. By analyzing the binding free energies of these different drugs, it is found that all of them bind strongly at the active site. Surprisingly, however, ribavirin and favilavir do not bind the nucleotide on the complementary

SUBMITTER: Bylehn F 

PROVIDER: S-EPMC7805600 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature