Systematic Analyses of the Resistance Potential of Drugs Targeting SARS-CoV-2 Main Protease.

ABSTRACT: Drugs that target the main protease (M^pro) of SARS-CoV-2 are effective therapeutics that have entered clinical use. Wide-scale use of these drugs will apply selection pressure for the evolution of resistance mutations. To understand resistance potential in M^pro, we performed comprehensive surveys of amino acid changes that can cause resistance to nirmatrelvir (Pfizer), and ensitrelvir (Xocova) in a yeast screen. We identified 142 resistance mutations for nirmatrelvir and 177 for ensitrelvir, many of which have not been previously reported. Ninety-nine mutations caused apparent resistance to both inhibitors, suggesting likelihood for the evolution of cross-resistance. The mutation with the strongest drug resistance score against nirmatrelvir in our study (E166V) was th

SUBMITTER: Flynn JM 

PROVIDER: S-EPMC11161032 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature