A strategy for evaluating potential antiviral resistance to small molecule drugs and application to SARS-CoV-2.

ABSTRACT: Alterations in viral fitness cannot be inferred from only mutagenesis studies of an isolated viral protein. To-date, no systematic analysis has been performed to identify mutations that improve virus fitness and reduce drug efficacy. We present a generic strategy to evaluate which viral mutations might diminish drug efficacy and applied it to assess how SARS-CoV-2 evolution may affect the efficacy of current approved/candidate small-molecule antivirals for M^pro, PL^pro, and RdRp. For each drug target, we determined the drug-interacting virus residues from available structures and the selection pressure of the virus residues from the SARS-CoV-2 genomes. This enabled the identification of promising drug target regions and small-molecule antivirals that the virus can deve

SUBMITTER: Sargsyan K 

PROVIDER: S-EPMC9831016 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature