Inhibittory mechanism of Ursolic Acid on HTLV-1 and HIV protease; an in silico study

HTLV-1 protease, a member of aspartic acid protease family, play an important role in maturation during virus replication cycle [1] . So far, various drugs have been designed and synthesized to control the HTLV-1, but unfortunately there is still no definitive treatment for the virus in the world. Experimental evidences showed that Ursolic Acid inhibit HIV protease [2 ,3]. In this study, molecular docking simulations applied to guess binding mode of Ursolic acid to HTLV protease (with 28% similarity with HIV protease). At first, 3D models of HIV and HTLV-1 protease (PDB code: 1YT9 and 3LIN) was optimized by Gromacs. To predict ligand-protein binding mode, Focused and Blind Docking were performed by Autodock [4]. Theoretical inhibition constant (ki):1.11 μM and inhibition constant (ki) 46.66 nM were obtained for the best binding modes of focused and blind docking, respectively. Ursolic Acid interacted to HTLV-1 protease via 2 hydrogen bonds (ARG10[2]) and via 1 hydrogen bonds (TYR114) in focused and blind docking, respectively. According to our results, Ursolic acid is able to interact with HTLV-1 protease as HIV protease. It proposes that the Ursolic acid and its derivatives potentially are good candidate to be developed as a novel inhibitor for HTLV-1 protease.

Keywords:

HTLV , 1 protease , HIV protease , Ursolic acid , Molecular docking , Drug design