Contributions of Hyperactive Mutations in M^pro from SARS-CoV-2 to Drug Resistance.

ABSTRACT: The appearance and spread of mutations that cause drug resistance in rapidly evolving diseases, including infections by the SARS-CoV-2 virus, are major concerns for human health. Many drugs target enzymes, and resistance-conferring mutations impact inhibitor binding or enzyme activity. Nirmatrelvir, the most widely used inhibitor currently used to treat SARS-CoV-2 infections, targets the main protease (M^pro) preventing it from processing the viral polyprotein into active subunits. Our previous work systematically analyzed resistance mutations in M^pro that reduce binding to inhibitors; here, we investigate mutations that affect enzyme function. Hyperactive mutations that increase M^pro activity can contribute to drug resistance but have not been thoroughly st

SUBMITTER: Flynn JM 

PROVIDER: S-EPMC11179160 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature