NS3 protease is an attractive target for development of antiviral agent. To gain more chemical insight for the molecular mechanism involved in the anti-HCV activity of pheophytin a, computational molecular modeling was performed by docking pheophytin a onto the active site of HCV NS3/4A. The best predicted binding mode was illustrated in Fig. 3A and B. The
Regorafenib HIS57, LYS136, SER139, and ALA155 were involved in the formation of four hydrogen bonding with pheophytin a. In addition, the amino acids SER42, GLY137, LYS136, VAL132, SER133, CYS159, PHE154, ALA156, ASP168, and ARG155 also contributed to the hydrophobic interactions and binding with pheophytin a. An important non-covalent
hydrogen bond interaction was formed between the hydroxyl group of SER139 of the NS3 catalytic triad and the acyl oxygen in the ester group of pheophytin a. Furthermore, the S1, S2, S3, and S4 sites of NS3 were probably occupied by the porphin group of pheophytin a, and the S′ sites other than S1′ were possibly occupied by a phytol group of pheothytin a. The particular hydrophobic interaction was formed between a phytol group of pheophytin a and a long nonpolar chain of four carbon atoms of LYS136. These data suggest that pheophytin a may have a functional interplay with HCV-NS3.
