Severe acute respiratory syndrome coronavirus main protease (Mpro (also known as 3CLpro))

The severe acute respiratory syndrome coronavirus main protease (Mpro, also called 3-chymotrypsin-like protease or 3CLpro) is a highly conserved cysteine hydrolase found in β-coronaviruses such as SARS-CoV and SARS-CoV‑2. It is responsible for cleaving the large viral polyproteins pp1a and pp1ab at more than 11 specific sites to generate functional nonstructural proteins essential for viral replication. Mpro’s unique structure—distinct from human host enzymes—makes it an attractive target for antiviral drug design because selective inhibition can block virus maturation without affecting human proteins. Several small-molecule inhibitors have been developed that act by covalently or non-covalently blocking its catalytic activity; nirmatrelvir is a clinically approved example used in COVID‑19 therapy. The enzyme’s essential role in the coronavirus life cycle underpins its status as a key therapeutic target during outbreaks such as COVID‑19[2][3][4][7].

Other names

Main protease3-chymotrypsin-like protease (3CLpro)Nsp5Coronavirus main cysteine protease

Covalent inhibition of the active site cysteine residue to block enzymatic activity; Non-covalent competitive inhibition at the substrate binding site