Picornain 3C (3C protease) (3Cpro)

The 3C protease (3Cpro), formally known as Picornain 3C, is an essential cysteine protease encoded by members of the Picornaviridae family, including Human Rhinovirus (HRV), Enterovirus 71, and Poliovirus (UniProt: P04936). It is responsible for the majority of the proteolytic processing of the viral polyprotein, cleaving it at specific Gln-Gly or Gln-Ser sites to generate mature structural and non-structural proteins necessary for viral replication (PubMed: 15155836). In addition to polyprotein processing, 3Cpro acts as a virulence factor by cleaving host cell proteins such as TATA-binding protein (TBP) and transcription factor IIIC, effectively shutting down host transcription and blunting the innate immune response (PubMed: 11466373). Because the substrate specificity of 3Cpro is distinct from human cellular proteases, it is considered a highly attractive target for antiviral therapy. Drugs like rupintrivir have been developed as irreversible peptidomimetic inhibitors to block the catalytic cysteine (Cys147 in HRV), though clinical challenges include delivery and the rapid development of viral resistance (PubMed: 12615902). While similar in function and fold to the 3C-like protease (3CLpro) of coronaviruses, Picornain 3C represents a distinct family of enzymes primarily associated with respiratory and enteric picornaviral diseases.

Other names

3C proteaseViral 3C proteasePicornavirus 3C proteaseHuman rhinovirus 3C proteaseEnterovirus 3C protease3C cysteine proteasePolypeptide 3C

Irreversible or reversible inhibition of the catalytic cysteine residue within the enzyme's active site, preventing the cleavage of the viral polyprotein and subsequent viral replication (PubMed: 11466373).