Drugs targeting the viral enzymes of SARS-CoV-2

The infectious coronavirus outbreak reported in Wuhan in 2019 became a pandemic. Owing to the similarity of the virus to severe acute respiratory syndrome-related coronavirus (SARS-CoV), the virus was named SARS-CoV-2. Enzymes like RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro), and papain-like protease (PLpro) catalyze reactions essential for viral amplification. These enzymes are promising drug targets for SARS-CoV-2 because they are viral products with no host cell homologs. For example, remdesivir (targets RdRp) and nirmatrelvir (targets 3CLpro) are currently available drugs for SARS-CoV-2. GRL-0617, a selective inhibitor of PLpro, binds to the ubiquitin-specific protease (USP) domain of PLpro and inhibits its substrate-binding activity. In this review, we provide information on current drugs targeting viral enzymes of SARS-CoV-2 and discuss the role of PLpro in the host immune response.