Rapid resistance profiling of SARS-CoV-2 protease inhibitors

  • bioRxiv. 2023 Feb 27:2023.02.25.530000. doi: 10.1101/2023.02.25.530000.
Seyed Arad Moghadasi  1 ,  Rayhan G Biswas  1 ,  Daniel A Harki  1 ,  Reuben S Harris  1  2
Affiliations
  • 1. University of Minnesota, Minneapolis, Minnesota, USA, 55455.
  • 2. Howard Hughes Medical Institute, University of Texas Health San Antonio, San Antonio, Texas, USA, 78229.
PMID: 36909573 DOI: 10.1101/2023.02.25.530000
Abstract

Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already exist in clinical SARS-CoV-2 isolates. Here a panel of SARS-CoV-2 main protease (Mpro) variants and a robust cell-based assay are used to compare the resistance profiles of nirmatrelvir, ensitrelvir, and FB2001. The results reveal distinct resistance mechanisms ("fingerprints") and indicate that these next-generation drugs have the potential to be effective against nirmatrelvir-resistant variants and vice versa.

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