3C-like protease and its inhibitors(PDB ID:6lu7, 7n89, 6wnp)


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 inhibitor N3 binds to the binding site of the substrate protein, to prevent substrate proteins to be cleaved and to prevent disease. Similarly, the inhibitor boceprevir can bind to the site and inhibit binding of substrate proteins. Many pharmaceutical companies are now developing inhibitor chamiecal compounds for this protein.

Surface chain 1 Surface chain 2 3C-like protease chain 1 3C-like protease chain 2 substrate protein inhibitor N3 inhibitor boceprevir
Turn stop Active site of 3C-like protease: 41H 145C Cleavage site of substrate protein; 5Q 6S