In vitro selection and analysis of SARS-CoV-2 nirmatrelvir resistance mutations contributing to clinical virus resistance surveillance.

ABSTRACT: To facilitate the detection and management of potential clinical antiviral resistance, in vitro selection of drug-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) against the virus M^pro inhibitor nirmatrelvir (Paxlovid active component) was conducted. Six M^pro mutation patterns containing T304I alone or in combination with T21I, L50F, T135I, S144A, or A173V emerged, with A173V+T304I and T21I+S144A+T304I mutations showing >20-fold resistance each. Biochemical analyses indicated inhibition constant shifts aligned to antiviral results, with S144A and A173V each markedly reducing nirmatrelvir inhibition and M^pro activity. SARS-CoV-2 surveillance revealed that in vitro resistance-associated mutations from our studies and those reported in t

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC11268423 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature