Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir

ABSTRACT

The SARS-CoV-2 main protease (M^pro) is a cysteine protease and a validated antiviral drug target. Paxlovid is an FDA-approved oral COVID-19 antiviral that contains the M^pro inhibitor nirmatrelvir and the metabolic booster ritonavir. The emergence of SARS-CoV-2 variants mutations in the M^pro raised the alarm of potential drug resistance. In this study, we aim to discover M^pro drug resistant mutants from naturally observed polymorphisms.

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