Severe acute respiratory syndrome coronavirus 2 3-chymotrypsin-like cysteine protease (3CLpro (also referred to as Mpro))

Severe acute respiratory syndrome coronavirus 2 3-chymotrypsin-like cysteine protease (3CLpro, also known as main protease or Mpro) is the essential enzyme encoded by SARS-CoV-2 and responsible for cleaving the large viral polyproteins (pp1a and pp1ab) at 11 specific sites to release mature nonstructural proteins vital for viral genome replication and transcription[1][2][4][5][6]. 3CLpro is a cysteine protease featuring a catalytic dyad of cysteine and histidine, and its activity is required for production of the virus[1][2][4][5]. As such, it is a major antiviral drug target, with approved inhibitors like nirmatrelvir (in Paxlovid) and numerous experimental molecules designed to irreversibly or competitively inhibit its enzymatic activity[6]. The protease is structurally characterized by three domains, requires dimerization for full activity, and exhibits strict substrate specificity for glutamine at the cleavage site[2][4]. 3CLpro does not have homologues in the human host, reducing potential for off-target toxicity and making it a preferred focus for anti-coronavirus therapeutic discovery and development.

Other names

3CLproMain proteaseMpro3C-like proteaseC30 endopeptidaseNonstructural protein 5 (nsp5)SARS-CoV-2 main proteinaseCoronavirus main protease

Covalent and non-covalent inhibition of the active site; Inhibition of catalytic activity (blocks cleavage of viral polyproteins required for virus maturation)[6]; Disruption of dimerization (some investigational strategies)[2]