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Rapid resistance profiling of SARS-CoV-2 protease inhibitors

View ORCID ProfileSeyed Arad Moghadasi, Rayhan G. Biswas, View ORCID ProfileDaniel A. Harki, View ORCID ProfileReuben S. Harris
doi: https://doi.org/10.1101/2023.02.25.530000
Seyed Arad Moghadasi
1University of Minnesota, Minneapolis, Minnesota, USA, 55455
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  • For correspondence: mogha019@umn.edu rsh@uthscsa.edu
Rayhan G. Biswas
1University of Minnesota, Minneapolis, Minnesota, USA, 55455
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Daniel A. Harki
1University of Minnesota, Minneapolis, Minnesota, USA, 55455
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Reuben S. Harris
1University of Minnesota, Minneapolis, Minnesota, USA, 55455
2Howard Hughes Medical Institute, University of Texas Health San Antonio, San Antonio, Texas, USA, 78229
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  • For correspondence: mogha019@umn.edu rsh@uthscsa.edu
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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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 27, 2023.
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Rapid resistance profiling of SARS-CoV-2 protease inhibitors
Seyed Arad Moghadasi, Rayhan G. Biswas, Daniel A. Harki, Reuben S. Harris
bioRxiv 2023.02.25.530000; doi: https://doi.org/10.1101/2023.02.25.530000
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Rapid resistance profiling of SARS-CoV-2 protease inhibitors
Seyed Arad Moghadasi, Rayhan G. Biswas, Daniel A. Harki, Reuben S. Harris
bioRxiv 2023.02.25.530000; doi: https://doi.org/10.1101/2023.02.25.530000

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