Middle East respiratory syndrome coronavirus main protease (MERS-CoV Mpro) (MERS-CoV Mpro)

The Middle East respiratory syndrome coronavirus main protease (MERS-CoV Mpro), also known as 3C-like protease (3CLpro), is a key enzyme required for the processing of the viral polyproteins pp1a and pp1ab (UniProt: P0C6S2). It cleaves these polyproteins at eleven sites to generate functional non-structural proteins (nsps) that are essential for the assembly of the viral replication-transcriptase complex (PubMed: 26147531). Mpro operates as a homodimer and utilizes a catalytic dyad consisting of Cys148 and His41 to perform its proteolytic function (PDB: 4YLU). Since no human proteases are known to share the same substrate specificity—specifically the requirement for glutamine at the P1 position—Mpro is considered an ideal target for antiviral drug design with a high safety profile (PubMed: 24130887). Therapeutic candidates, such as the peptidomimetic inhibitor GC376, aim to bind the active site and prevent the maturation of viral proteins, thereby stopping viral replication (PubMed: 32573555). This target remains a focal point for developing broad-spectrum coronavirus treatments due to its conserved nature across different lineages (PubMed: 26147531).

Other names

3C-like protease3CLproNon-structural protein 5nsp5MERS-CoV 3CLpro

Inhibition of the proteolytic cleavage of viral polyproteins pp1a and pp1ab, thereby preventing the assembly of the viral replication-transcriptase complex.