Enterovirus 71 3C protease (EV71 3Cpro)

Enterovirus 71 (EV71) 3C protease is a critical chymotrypsin-like cysteine protease required for the replication and pathogenesis of the virus (UniProt: P04585). It is primarily responsible for the proteolytic processing of the viral polyprotein into mature structural and non-structural proteins, a step essential for viral assembly (PMID: 21471240). Beyond its role in replication, the 3C protease actively subverts the host immune system by cleaving key signaling molecules involved in the type I interferon pathway, such as RIG-I, TRIF, and MAVS (PMID: 21835794). This dual role makes it an attractive therapeutic target for treating Hand, Foot, and Mouth Disease (HFMD) and its severe neurological complications like encephalitis (PMID: 25101577). Drug development efforts have focused on peptidomimetic inhibitors like Rupintrivir, which covalently bind to the active site cysteine (PMID: 28834146). However, challenges remain regarding the emergence of drug-resistant viral strains and the need for high specificity to avoid inhibiting host cellular proteases. Effective inhibition of this enzyme could potentially reduce viral load and prevent the progression to life-threatening neurological or pulmonary symptoms.

Other names

EV-A71 3C protease3C cysteine proteaseEnterovirus A71 3C protease3Cpro

Covalent or non-covalent inhibition of the catalytic cysteine residue (Cys147), preventing polyprotein cleavage and viral maturation (PMID: 21471240).