Marine derivatives prevent E6 protein of HPV: An in silico study for drug development

Abstract

Cervical cancer (CC) is one of the most common cancers in women worldwide in which most cases are diagnosed with the Human Papilloma Virus (HPV). At the present time, there is neither a vaccine nor a drug to prevent or to effectively treat HPV infection. In the recent decades, compounds originated from marine organisms are well known for their novel chemical structures and wide range of biological activities. In the frame of our ongoing program to identify natural compounds endowed with anticancer bioactivities, this study conducted in silico assessment of 502 compounds originated from marine organisms against E6 protein of HPV for potential inhibition activity. The tertiary structure of targeted protein was constructed using SWISS-MODEL in which obtained Ramachandran plot proved the high quality of the protein model with 87.7% residues located in the most favored region and 11.6% residues allocated in the allowed region. All studied compounds were evaluated for drug-like and pharmacokinetic properties. AutoDock 4.2.6 and AutoDock Vina 1.2.0 were utilized to investigate the docking conformation of studied compounds towards E6 protein. High correlation coefficient between the dock score of AutoDock 4.2.6 and AutoDock Vina 1.2.0 was recorded with the value of R = 0.62. Docking outcomes in combination with ADMET studies identified compounds 153, 185 and 500 are the top “hits” for further drug development based on dock score ranking and docking conformation analysis, in particularly, compound 153 could be considered with caution due to its potent in causing mutation.