Molecular Landscape and Computational Screening of the Natural inhibitors against HPV16 E6 Oncoprotein

BACKGROUND: Human Papillomavirus (HPV) is a small, non-enveloped, icosahedral and double-stranded DNA virus with a genome of 8 kb, belonging to the papillomaviridae family. HPV has been associated with 99.7% cases of cervical squamous cell carcinoma worldwide. The HPV E6 protein is known as a potent oncogene and is closely allied with the events that result in the malignant transformation of virally infected cells. OBJECTIVE: The present study aims to target plant derived anticancer molecules for HPV driven cancer using a computational approach. Methods: In this study, E6 oncoprotein was targeted by 101 plant-derived nutraceuticals using the molecular docking method. The multiple sequence analysis and phylogenetic analysis of low risk and high risk 28 HPV E6 proteins were performed. RESULTS: Withanolide D, Ginkgetin, Theaflavin, Hesperidin, and Quercetin-3-gluconide were identified as the potential inhibitors of HPV 16 E6 protein. The zinc finger domain was identified on all variants of HPV E6 oncoprotein while high-risk HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV58, HPV68 and HPV73: probable risk HPV53 and low-risk HPV43 and HPV70 contain PDZ domain. CONCLUSION: The current study using bioinformatics analysis approaches reveals a promising platform for developing anti-cancerous competitive inhibitors targeting HPV.