title: In Silico Docking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly Threatening Human Papillomavirus 18.
abstract: The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Lingaraja
authors.initials: L
authors.lastname: Jena
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Maheswata
authors.initials: M
authors.lastname: Sahoo
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Mrunmayi
authors.initials: M
authors.lastname: Kakde
authors.affiliation: Obstetrics & Gynaecology, Datta Meghe Institute of Medical Sciences (Deemed University), Nagpur 440-022, India.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Daf
authors.affiliation: Advanced Centre for Treatment, Research & Education in Cancer, Navi Mumbai 410-210, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Varma
keywords: human papillomavirus 18; molecular docking; neoplasms; plant products