Coronaviruses (CoVs) are positive-stranded RNA viruses that can infect humans and multiple species of animals, causing a wide spectrum of diseases [E1]. The CoV replicase gene encodes two overlapping polyproteins, termed pp1a and pp1ab, which mediate viral replication and transcription. The maturation of CoVs involves a highly complex cascade of proteolytic processing events on the polyproteins to control viral gene expression and replication. Most maturation cleavage events within the precursor polyprotein are mediated by a viral cysteine proteinase which is called the 'main proteinase' (M-pro) or, alternatively, the '3C-like proteinase' (3CL-pro). The ~300-residue mature form of the M-pro is released from pp1a and pp1ab by autoproteolytic cleavage and employs conserved cysteine and histidine residues in the catalytic site [1,2,3,4]. It belongs to peptidase family C30 [E2].

The CoV M-pro comprises three domains (see <PDB:1LVO>). Domains I and II are six-stranded antiparallel β barrels and together ressemble the architecture of chymotrypsin and of picornaviruses 3C proteinases. The substrate-binding site is located in a cleft between these two domains. The catalytic site is situated at the center of the cleft. A long loop connects domain II to the C-terminal domain (domain III). This latter domain, a globular cluster of five helices, has been implicated in the proteolytic activity of M-pro. In the active site of M-pro, Cys and His form a catalytic dyad. In contrast to serine proteinases and other cysteine proteinases, which have a catalytic triad, there is no third catalytic residue present [1,2,3,4].

The profile we developed covers the entire M-pro domain.