Investigation of potential antiviral natural products with an effect on HPV18 E6 protein by molecular docking method

Abstract

Background: Infection with the Human Papillomavirus (HPV) causes cellular dysplasia, which leads to cervical cancers in women and penile or rectal cancers in men. Objective: This in silico study identified the plant compounds with potential therapeutic effects against HPV 18 oncogenic virus using the molecular docking method. Methods: The three-dimensional (3D) structure of HPV18 E6 protein, as the target protein, and the 3D structure of plant compounds with potential therapeutic effect against viruses, as ligands, was obtained from the protein databases (RCSB) and PubChem, respectively. Both structures of ligands and target protein were subjected to AutoDock tools-1.5.6, ver.4 separately. The structure with the most negative affinity was docked to reconsider its connection location. The results were analyzed more based on pharmacodynamic and pharmacokinetic parameters. Results: The docking of HPV18 E6 protein with 19 selected ligands resulted in four compounds, curcumin, silymarin, saikosaponin c, and lactupicrin, showing the best docking scores; they had better binding free energies with HPV E6 protein. Among four compounds against HPV18 E6, silymarin and curcumin were less dangerous than other compounds due to the lack of inhibition of the human Ether-à-go-go-Related Gene (hERG). Of these two compounds, silymarin had lower oral absorption, lactopicrin had less skin absorption, lactopicrin is the substrate of P-gp, and saikosaponin c crosses the blood-brain barrier. Conclusion: Among potential antiviral plants against HPV18E6, four compounds were found to be effective. According to these findings, it is recommended that in vitro and in vivo examinations be conducted to determine the effectiveness of these compounds against HPV18 Keywords: Biological products, Antiviral agents, HPV18, Molecular docking, Computational biology, E6 protein

Structure-Based Discovery of Potential HPV E6 and EBNA1 Inhibitors: Implications for Cervical Cancer Treatment

“…A previous study docked 12 natural products with known anti-HPV activity against the HPV18 E6 protein using Autodock 4.2, and their docking scores ranged from −2.86 to −5.85 kcal/mol [101]. Another study also docked known antivirals (natural products) against the HPV18 E6 protein using Autodock 4.2, and the docking scores of the top 19 compounds ranged from −7.48 to −14.77 kcal/mol [102]. Also, doxorubicin and pinoresinol monomethyl ether-β-Dglucoside (PMG), isolated from the dichloromethane extract of Jurinea macrocephala subsp.…”