Computational investigation of marine bioactive compounds against E6 oncoprotein of Human Papilloma Virus-HPV16

Objective: Cervical cancer is the most leading cause of mortality and morbidity in women. Most of these are caused by human papilloma virus (HPV) which are sexually transmitted. Among 200 HPV types, high-risk HPV16 persists in humans and results in precancerous lesions and cervical cancer. The viral E6 oncoprotein which is necessary for malignant conversion of HPV 16 is used as the potential target for the inhibition of HPV infection. The present study aims to investigate the inhibitory activities of the seventy-four bioactive compounds from different marine organisms against the viral E6 oncoprotein of HPV16 using computational techniques. Methods: Virtual screening technique has been applied to identify the potent bioactive compounds against E6 oncoprotein of HPV16 using Molinspiration and is subjected to drug-likeliness assessment using the Molsoft server. Molecular docking was carried out for E6 protein (4XR8) with selected hits obtained from virtual screening method and their binding energies were determined. Further Molecular Dynamic Simulation (MDS) studies of the obtained protein-bioactive inhibitor complex were performed to analyze the stability and conformation. Results and Conclusion: Four potential hits were identified from virtual screening and finalized against HPV16. Molecular docking studies revealed Salicylihalamide B from Haliclona species has shown the better interaction with E6 oncoprotein and gives the best binding energy of -8.92 Kcal/mol. The MDS studies inferred that the complex was found to be steady after 40 ns. As an outcome, Salicylihalamide B plays a promising role against E6 protein of HPV16 and hence can act as a template for further studies on cervical cancer drug candidates.