Computational design of E6 protein inhibitors‏ ‏for the treatment ‎of HPV16 disease

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide, and high-risk HPV types cause about five percent of all cancers worldwide. The chemical drugs used to treat this disease are expensive and have many side effects. Therefore, the use of herbal medicines is increasing. In this regard, the E6 protein, which is a key protein in the initiation of cervical cancer and plays a role in the degradation of P53, was selected as an essential drug target. In this research, two new potential inhibitors named beta-sitosterol (CID_222284) and loncocarpenin (CID_54699185) were identified as potent inhibitors of E6 HPV-16 from the PubChem library by high-throughput virtual screening. Molecular dynamics results show that these compounds bind to E6 protein with high stability. The preparation of ADMET and Swiss ADME profiles indicates that the identified compounds are probably potential candidates against E6 HPV-16 and can be used in chemotherapy by inhibiting the Pgp channel as an adjuvant drug.