Antiviral activity of hydrazone derivatives based benzohydrazide/2-thiohydantoin analogs against HPV-18 (Human papillomavirus): In silico study

Abstract

The prevalence of cervical cancer remains at the top of the rankings in the world threatening millions of women's lives, especially in Indonesia. However, the growth of cervical cancer can be prevented in the presence of compounds with good and antiviral activity. This study was performed in silico by binding a hydrazone ligands molecule to the HPV-18 (Human papillomavirus) (ID: 6ZFD) on the A chain. The ligand compounds were first drawn with 3D structures using Avogadro then geometric optimization and frequency calculations were carried out with B3LYP/6-31G* using Gaussian 16. Molecular docking is carried out specifically on a predetermined binding site with a grid box size and spacing is 40 x 40 x 40 and 0.5, respectively and performed on Autodock4 1.5.7 Tools. The best docking results were obtained in the ligand-protein complex of the Pythbenz ligand with affinity energy and inhibition constant are -7.88 kcal/mol and 1.69 µM, respectively. Visualization analysis of docking results were performed using the web servers PLIP Tools, LigPlot, and PyMOL which provided information on the interaction of residual amino acids formed and drug score from each ligand-protein complex. Based on the results of the analysis, the complex compound hydrazone-derived ligand-protein has the potential to be antiviral drug in cervical cancer.