Main protease of SARS-CoV-2 (also known as 3C-like protease) (Mpro or 3CLpro)

The main protease of SARS-CoV-2, often referred to as Mpro or 3CLpro, is a cysteine protease that plays a critical role in the viral life cycle by cleaving viral polyproteins (pp1a and pp1ab) into non-structural proteins essential for replication and transcription of the viral genome[1][2][3][4]. This enzyme is highly conserved among coronaviruses, contains a catalytic dyad formed by cysteine and histidine residues, and recognizes specific amino acid sequences at multiple cleavage sites, performing proteolysis vital for generating the viral replication-transcription complex[1][3][4][6]. Because of its indispensable functional role and absence of closely related proteases in humans, Mpro is a prime therapeutic target for COVID-19 antiviral drug development[2][3][6]. Multiple small molecule inhibitors, including the clinically approved nirmatrelvir, specifically target and inhibit Mpro by binding to its active site and preventing polyprotein processing, thus blocking viral replication[6]. Notable safety concerns include the potential for viral resistance mutations and off-target effects due to inhibitor interaction with human cellular proteases[6].

Other names

3C-like protease3CLproMain proteasensp5SARS-CoV-2 proteaseSARS coronavirus 2 main protease

Inhibition of protease activity leading to prevention of viral polyprotein cleavage and thereby inhibition of viral replication