3C-like protease and its inhibitors

(PDB ID:6lu7, 7n89, 7rfs, 7vu6)

A coronavirus enzyme, 3C-like protease is composed of two identical proteins (cyan and magenta). The corona virus make us to synthesize a very long protein with 7096 amino acids, polyprotein 1ab. Polyprotein 1ab then is broken into 15 pieces of proteins. One of the proteases to break the polyprotein 1ab, is this 3C-like protease. The substrate protein (yellow) is a part of the polyprotein 1ab; only 8 residues are extracted from the 7096 amino acids (3269-3266). The cleavage site is between the 5-th (5Q) and the 6-th (6S) residue. The 3C-like protease is a potential drug target for covid-19. For example, the antiviral drug Paxlovid (Nirmatrelvir) binds to the binding site of the substrate protein, to prevent substrate proteins to be cleaved and to prevent disease. Similarly, the inhibitor Xocova (Ensitrelvir) can bind to the site and inhibit binding of substrate proteins. Many pharmaceutical companies are now developing chemical compounds to block this protein.

Active site of 3C-like protease: Cleavage site of substrate protein: