A comprehensive study of SARS-CoV-2 main protease (M^pro) inhibitor-resistant mutants selected in a VSV-based system.

ABSTRACT: Nirmatrelvir was the first protease inhibitor (PI) specifically developed against the SARS-CoV-2 main protease (3CL^pro/M^pro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir. To safely generate M^pro resistance mutations, we passaged a previously developed, chimeric vesicular stomatitis virus (VSV-M^pro) with increasing, yet suboptimal concentrations of nirmatrelvir. Using Wuhan-1 and Omicron M^pro variants, we selected a large set of mutants. Some mutations are frequently present in GISAID, suggesting their relevance in SARS-CoV-2.

SUBMITTER: Costacurta F 

PROVIDER: S-EPMC10557589 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature