Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.

ABSTRACT: Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (M^pro), its moderate activity in M^pro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin's efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that

SUBMITTER: Reinke PYA 

PROVIDER: S-EPMC10584882 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature