Key dimer interface residues impact the catalytic activity of 3CLpro, the main protease of SARS-CoV-2.

ABSTRACT: 3C-like protease (3CLpro) processes and liberates functional viral proteins essential for the maturation and infectivity of severe acute respiratory syndrome coronavirus 2, the virus responsible for COVID-19. It has been suggested that 3CLpro is catalytically active as a dimer, making the dimerization interface a target for antiviral development. Guided by structural analysis, here we introduced single amino acid substitutions at nine residues at three key sites of the dimer interface to assess their impact on dimerization and activity. We show that at site 1, alanine substitution of S1 or E166 increased by twofold or reduced relative activity, respectively. At site 2, alanine substitution of S10 or E14 eliminated activity, whereas K12A exhibited ∼60% relative activity. At site 3, alanine

SUBMITTER: Ferreira JC 

PROVIDER: S-EPMC9091064 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature