Identification of Novel Inhibitors Against HPV16/18-E7 for Cancer Therapy

摘要

Cervical cancer contributes most to cancer mortality in women worldwide. Human Papilloma Virus (HPV) is majorly involved in progression of cervical cancer through E7 oncoprotein directed inhibition of Retinoblastoma tumour suppressor protein (pRB). Studies reported E7 proteins of HPV16/18 (HPV16/18-E7) as potential targets for identification of lead compounds. Generally, HPV16/18-E7 participates in the process of cell proliferation and metastasis of cancer, indicates its functional similarity with human cellular kinases. Despite of various efforts, until there is no establish inhibitor reported for HPV16/18-E7 target. Current study examine the inhibition proficiency of well-known kinase inhibitors for the control of HPV16/18-E7 function through molecular modelling, virtual screening. Top six inhibitors for both strains HPV16/18-E7 examined and CID9549298 inhibitor showing highest inhibition efficiency against both strains can be referred as multi-target inhibitor. However, CID5329102, CID5749625, CID6818961 and CID641974 also shows good inhibition efficacy to HPV16-E7 and HPV18-E7. Furthermore, the effects of these inhibitors in various proteins involved in different biological process and metabolic pathways responsible for cell proliferation were explored. We do believe that findings can be further helpful towards inhibition of cervical cancer growth through in-vitro and in-vivo experiments.