Multiple redox switches of the SARS-CoV-2 main protease in vitro provide opportunities for drug design.

ABSTRACT: Besides vaccines, the development of antiviral drugs targeting SARS-CoV-2 is critical for preventing future COVID outbreaks. The SARS-CoV-2 main protease (M^pro), a cysteine protease with essential functions in viral replication, has been validated as an effective drug target. Here, we show that M^pro is subject to redox regulation in vitro and reversibly switches between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues. These include a disulfide-dithiol switch between the catalytic cysteine C145 and cysteine C117, and generation of an allosteric cysteine-lysine-cysteine SONOS bridge that is required for structural stability under oxidative stress conditions, such as those exerted by the innate immune s

SUBMITTER: Funk LM 

PROVIDER: S-EPMC10776599 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature