An Investigation of Nirmatrelvir (Paxlovid) Resistance in SARS-CoV-2 M^pro.

ABSTRACT: The high throughput YESS 2.0 platform was used to screen a large library of SARS-CoV-2 M^pro variants in the presence of nirmatrelvir. Of the 100 individual most prevalent mutations identified in the screen and reported here, the most common were E166V, L27V, N142S, A173V, and Y154N, along with their various combinations. In vitro analysis revealed that resistance to nirmatrelvir for these individual mutations, as well as all of the combinations we analyzed, was accompanied by decreased catalytic activity with the native substrate. Importantly, the mutations we identified have not appeared as significantly enriched in SARS-CoV-2 M^pro sequences isolated from COVID-19 patients following the introduction of nirmatrelvir. We also analyzed three of the most common SA

SUBMITTER: Yaghi RM 

PROVIDER: S-EPMC11659887 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature