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Interdiscip Sci. 2015 Feb 6. [Epub ahead of print]

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

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Biochemistry & Bioinformatics Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, India,


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.


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