SARS-CoV-1 main protease (Mpro)

The SARS-CoV-1 main protease (Mpro), also known as 3C-like protease (3CLpro) or nsp5, is a critical enzyme for the life cycle of the Severe Acute Respiratory Syndrome coronavirus [1][3]. It is responsible for processing the large polyproteins (pp1a and pp1ab) translated from the viral RNA into functional non-structural proteins (nsps) essential for viral replication and transcription [3][17]. The enzyme operates as a homodimer and utilizes a catalytic dyad consisting of His41 and Cys145 to cleave the polyprotein at 11 conserved sites [3][8]. Because no human proteases share the same cleavage specificity (preferring Glutamine at the P1 position), it is a highly attractive target for antiviral drug development [1][10]. Inhibitors of this protease, such as those developed during the SARS and subsequent COVID-19 outbreaks, aim to block the active site, thereby halting the production of infectious progeny [2][16]. Therapeutic challenges include ensuring high selectivity to avoid host toxicity and managing the potential for viral resistance through mutations in the substrate-binding pockets [6][16].

Other names

3C-like protease3CLpronsp5Non-structural protein 5C30 endopeptidase

Inhibition of the catalytic cysteine residue (Cys145) within the active site, preventing the proteolytic processing of viral polyproteins pp1a and pp1ab into functional non-structural proteins [2][5][14].