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Rapid resistance profiling of SARS-CoV-2 protease inhibitors.

Reuben Stewart HarrisSeyed MoghadasiRayhan G BiswasDaniel A Harki
Published in: Research square (2023)
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.
Keyphrases
  • sars cov
  • respiratory syndrome coronavirus
  • single cell
  • copy number
  • gene expression
  • high throughput
  • stem cells
  • climate change
  • genome wide
  • mesenchymal stem cells