Viral 3C protease (3Cpro) (3Cpro)

Viral 3C protease is a critical chymotrypsin-like cysteine protease encoded by viruses in the Picornaviridae family, including human rhinovirus, poliovirus, and enterovirus 71 (UniProt, 2023). Its primary biological role is the site-specific cleavage of the viral polyprotein into mature structural and non-structural proteins, a step that is indispensable for viral replication and the assembly of new virions (PubMed, 2021).\n\nIn addition to its role in the viral life cycle, the 3C protease targets and degrades various host cell proteins, such as TATA-binding protein and poly(A)-binding protein, to shut down host cell transcription and translation, thereby facilitating viral dominance and immune evasion (Wikipedia, 2024). Because the enzyme's substrate preference for glutamine at the P1 position is not shared by human cellular proteases, it represents a highly selective target for antiviral drug design (NCBI PubChem, 2024). Therapeutic agents like rupintrivir (AG7088) are designed as peptidomimetic inhibitors that covalently bind to the active site cysteine, effectively halting the progression of viral infections (Matthews et al., 1999). While primarily associated with picornaviruses, the 3C-like protease (3CLpro) found in coronaviruses shares significant structural and functional similarities, making this class of enzymes a cornerstone of modern antiviral research (Zhang et al., 2020).

Other names

3C protease3C cysteine proteasePicornain 3C3CLproMain proteaseMpro

Inhibition of the viral protease activity by binding to the active site (often covalently to the catalytic cysteine residue), preventing the cleavage of the viral polyprotein into functional units (NCBI PubChem, 2024).