Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir.

ABSTRACT: Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19 (refs. ^1,2). However, because SARS-CoV-2 has evolved to become resistant to other therapeutic modalities^3-9, there is a concern that the same could occur for nirmatrelvir. Here we examined this possibility by in vitro passaging of SARS-CoV-2 in nirmatrelvir using two independent approaches, including one on a large scale. Indeed, highly resistant viruses emerged from both and their sequences showed a multitude of 3CL protease mutations. In the experiment peformed with many replicates, 53 independent viral lineages were selected with mutations observed at 23 different residues of the enzyme. Nevertheless, several common mutational pat

SUBMITTER: Iketani S 

PROVIDER: S-EPMC9849135 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature