Regulation of the Dimerization and Activity of SARS-CoV-2 Main Protease through Reversible Glutathionylation of Cysteine 300.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for coronavirus disease 2019 (COVID-19), encodes two proteases required for replication. The main protease (M^pro), encoded as part of two polyproteins, pp1a and pp1ab, is responsible for 11 different cleavages of these viral polyproteins to produce mature proteins required for viral replication. M^pro is therefore an attractive target for therapeutic interventions. Certain proteins in cells under oxidative stress undergo modification of reactive cysteines. We show M^pro is susceptible to glutathionylation, leading to inhibition of dimerization and activity. Activity of glutathionylated M^pro could be restored with reducing agents or glutaredoxin. Analytical studies dem

SUBMITTER: Davis DA 

PROVIDER: S-EPMC8406260 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature