Virtual screening for potential inhibitors of high-risk human papillomavirus 16 E6 protein

Abstract

Human papillomavirus (HPV), a life-threatening infection is the leading cause of cancer mortality among women worldwide and needs for designing anti-cancerous drugs. In the present study, we explored specific novel inhibitors against E6 onco-protein of high risk HPV 16, known to inactivate tumor suppressor p53 protein. A homology model of HPV 16 E6 was built and validated using bioinformatics approach. A total of 5000 drug like compounds were downloaded from ZINC database based on the properties similar to the known inhibitor Jaceosidin (5, 7-Dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-6-methoxy-4H-chromen-4-one). Virtual-ligand-screenings approaches were applied to screen appropriate drug like compounds using molecular docking program Auto Dock Vina in PyRx 0.8 and 5 best novel drug-like compounds were identified as potential competitive inhibitors against HPV 16 E6 compared to Jaceosidin. Two amongst these 5 identified most potential inhibitors, N-[(5-methyl-1Hbenzimidazol-2-yl)methyl]-4-oxo-3, 4-dihydrophthalazine-1-carboxamide and 6-[3-(3-fluoro-4-methyl-phenyl)-1, 2, 4-oxadiazol-5-yl]-1, 4-dihydroquinoxaline-2, 3-dione were found to interact with E6 with binding energy of -7.7 and -7.0 Kcal/mol respectively and form H-bonds with p53 binding site of E6 protein residues 113-122 (CQKPLCPEEK). These two inhibitors may help restoration of p53 functioning. The Bioinformatics approach extends a promising platform for developing anti-cancerous competitive inhibitors targeting high-risk HPV 16.

The in Silico Approach to Identifying a Unique Plant-Derived Inhibitor Against E6 and E7 Oncogenic Proteins of High-Risk Human Papillomavirus 16 and 18

“…The active site of the model was analyzed based on the docking interaction between the p53 and pRb binding site residues (12)(13)(14)(18)(19)(20) of HPV oncoproteins, and all natural ligands.…”

Virtual screening for potential inhibitors of β(1,3)-D-glucan synthase as drug candidates against fungal cell wall

“…Detection, evaluation, and development of novel efficient and safe drug candidates with a sufficient inhibitory function against pathogens are essential in the pharmaceutical industry. Overall, agents that are able to block the ligand binding sites of a receptor can be considered interesting potential inhibitors against the desirable receptor 47 . Hence, the introduced lead molecules in this study may be evaluable candidates for investigation through wet-lab analysis and could be potential inhibitors against 1,3-b-D-glucan synthase.…”

Identification of a Potential Target of Capsaicin by Computational Target Fishing

“…Molecular docking is a computational procedure that attempts to predict noncovalent binding of macromolecules or a macromolecule (receptor) and a small molecule (ligand) efficiently [ 17 ]. Autodock Vina in PyRx 0.8 is a new program for molecular docking and virtual screening that has been widely used [ 17 – 19 ].…”