Rapid resistance profiling of SARS-CoV-2 protease inhibitors

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

doi:10.21203/rs.3.rs-2627723/v1

Rapid resistance profiling of SARS-CoV-2 protease inhibitors

Res Sq [Preprint]. 2023 Mar 15:rs.3.rs-2627723. doi: 10.21203/rs.3.rs-2627723/v1.

Authors

Seyed Arad Moghadasi¹, Rayhan G Biswas¹, Daniel A Harki¹, 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.

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 (M^pro) 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.

Publication types

Preprint

Grants and funding

U19 AI171954/AI/NIAID NIH HHS/United States