Replication of SARS-CoV-2, the coronavirus causing COVID-19, requires a main protease (Mpro) to cleave viral proteins. Consequently, Mpro is a target for antiviral agents. We and others previously demonstrated that GC376, a bisulfite prodrug with efficacy as an anti-coronaviral agent in ...
Here we show that the feline antiviral prodrug GC376 is reversible and inhibits Mpro of both SARS-CoV and SARS-CoV-2 with low nanomolar Ki values. While IC50 values, the concentration of inhibitor at half-maximal inhibition, are very useful during drug development,41 Ki values describe precise...
All potent SARS-CoV-2 Mpro inhibitors contain reactive warheads such as α-ketoamide (boceprevir (28), calpain inhibitor XII (62)) or aldehyde (MG-132 (43), calpain inhibitor II (61)) or aldehyde prodrug, the bisulfite (GC-376 (64)). This result suggests that reactive warheads might ...