Middle East respiratory syndrome coronavirus 3C-like protease (MERS-CoV 3CLpro)

The Middle East respiratory syndrome coronavirus 3C-like protease (MERS-CoV 3CLpro), also known as the main protease (Mpro) or nsp5, is a key enzyme required for the maturation of the virus (UniProt: P0C6F2). It mediates the proteolytic processing of the large replicase polyproteins (pp1a and pp1ab) at eleven distinct sites, releasing essential non-structural proteins required for the formation of the viral replication-transcription complex (PubMed: 25111400). Structurally, the enzyme functions as a homodimer, where each monomer contains a catalytic dyad consisting of Cys148 and His41 (PubMed: 23861520). Because 3CLpro recognizes a specific substrate sequence (Leu-Gln↓Ser/Ala/Gly) that is not utilized by human host proteases, it serves as an ideal target for highly selective antiviral therapy (PubMed: 32454408). Small molecule inhibitors, such as the peptidomimetic GC376, have demonstrated potent activity by covalently binding to the active site cysteine, thereby halting viral replication (PubMed: 32843445).

Other names

Main proteaseMproNon-structural protein 5nsp5C30 endopeptidase

Inhibition of the 3C-like protease prevents the cleavage of viral polyproteins into functional non-structural proteins, thereby halting viral replication.