Virtually screened inhibitors for Human Papilloma Virus infections

Abstract Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. The current treatment methods consist of the use of chemotherapeutic agents or the application of surgical procedures to remove the developed tumors. The alternatives to treat HPV- associated diseases is the discovery of accessible drug-based therapies. In HPV infected cell, E6 protein complexes with E6AP to form p53 degradation complex and induce tumorigenesis. The objective of this study is to discover potential small molecule inhibitors against HPV16 E6 protein using virtual screening approach. Three novel HPV 16 E6 inhibitors viz. compound 5, compound 7 and compound 10 were designed using a fragment-based approach. The structural information of these three novel compounds was used in virtual screening against in- trials subset of ZINC database and a total of 9800 hits were identified. The obtained molecules from the database were further screened by three stages of virtual screening using GLIDE module of Schrodinger software. The results reveal that Five hit molecules (ZINC000034853956, ZINC000001534965, ZINC000095617673, ZINC000005764481 and ZINC000071606215) showed better glide score in comparison with reference molecule, Luteolin. These molecules exhibited crucial interactions with E6 protein of HPV 16. The pharmacokinetic properties of these hit molecules were analyzed using QikProp program. The results indicate that all the five molecules were found to have good pharmacokinetic properties and human oral absorption. All the five hit molecules were predicted to be no toxic and except ZINC000005764481, all other four molecules showed druglike behavior. Therefore, the four hit molecules (ZINC000034853956, ZINC000001534965, ZINC000095617673 and ZINC000071606215) can be used as lead molecules in the development of HPV 16 E6 inhibitors for treatment of HPV related diseases.