Rapid resistance profiling of SARS-CoV-2 protease inhibitors

Seyed Arad Moghadasi; Rayhan G Biswas; Daniel A Harki; Reuben S Harris

doi:10.1038/s44259-023-00009-0

Rapid resistance profiling of SARS-CoV-2 protease inhibitors

NPJ Antimicrob Resist. 2023 Aug 20;1(1):9. doi: 10.1038/s44259-023-00009-0.

Authors

Seyed Arad Moghadasi¹, Rayhan G Biswas¹, Daniel A Harki¹, Reuben S Harris^{2

3}

Affiliations

¹ University of Minnesota, Minneapolis, 55455, MN, USA.
² Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, 78229, TX, USA. rsh@uthscsa.edu.
³ Howard Hughes Medical Institute, University of Texas Health San Antonio, San Antonio, 78229, TX, USA. rsh@uthscsa.edu.

Abstract

Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already exist in clinical SARS-CoV-2 isolates. Here a robust cell-based assay is used to determine the relative potencies of nirmatrelvir, ensitrelvir, and FB2001 against a panel of SARS-CoV-2 main protease (M^pro) variants. The results reveal that these three drugs have at least partly distinct resistance mutation profiles and raise the possibility that the latter compounds may be effective in some instances of Paxlovid resistance and vice versa.

Abstract

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