SARS-CoV-2 3-chymotrypsin-like protease (3CLpro)

SARS-CoV-2 3-chymotrypsin-like protease (3CLpro, main protease) is a viral cysteine protease responsible for cleavage of the coronaviral polyproteins into functional nonstructural proteins essential for viral transcription, replication, and recombination. It features a catalytic dyad (His41 and Cys145), recognizes specific peptide sequences, and is indispensable in the viral life cycle. Because it is absent from human cells, it is an attractive drug target; numerous inhibitors have reached preclinical, clinical, and approved stages for COVID-19 treatment. Structural studies have revealed both active and allosteric sites, guiding drug discovery efforts for highly selective and potent antivirals. Resistance mutations have been reported, underlining the need for continued therapeutic innovation.

Other names

3C-like protease3CLproMain protease (Mpro)SARS coronavirus main proteinaseC30 endopeptidaseNonstructural protein 5 (nsp5)

Inhibition of proteolytic cleavage of viral polyproteins; Blocking enzymatic active sites or allosteric sites, preventing release of functional viral proteins; Both covalent and non-covalent inhibitor mechanisms reported