Mpro, 3CL is a critical enzyme for the virus life cycle. It activity yield non-structural proteins that are crucial for genome replication and Coronavirus virion production: RNA-dependent RNA polymerase, a helicase, ribonucleases and 3CLpro itself, from two types of polyproteins (pp1a and pp1ab).The maturation of SARS-Cov2 virus (SARS coronavirus) depends on cleavage of the overlapping large polyproteins 1a and 1ab by two viral proteases:
- Mpro (main protease)
- PLpro (Papain-like protease)
SARS-CoV Mpro, 3CL exists as a homodimer and each protomer has an active site. The proteolytic cleavage of 1ab polyprotein by Mpro occurs at 11 sites: 7 sites within the 1a polyprotein, and 11 sites within the 1ab polyprotein. This results in maturation of 16 viral non-structural proteins.Mpro protease forms a functional homodimer. Both the N-terminus and the C- terminus of Mpro have been shown to be critical for dimer formation and for enzyme function.
The Mpro protease, 3CLpro is an ideal target for antiviral drug design due to its high conservation between different coronavirus strains and absence of functional analogs in the human proteome. Mpro protease from SARS-CoV1 and SARS-CoV2 are functionally identical.