Antivirals for Herpes Simplex Virus 2 from Polygonum aviculare

Abstract

Genital herpes is a STD caused by HSV-2, infecting about 491 million people aged 15-49 (13%) worldwide (WHO). Lack of vaccine and development of resistant strains against first line drug Acyclovir has resulted in an urgent need to produce new antivirals. In this context, Polygonum aviculare has an ethnopharmacological use documented in De Materia Medica, as treatment of Genital Herpes, the scientific validation for which was lacking. We selected 42 phytochemicals of Polygonum aviculare and 10 viral proteins and carried out Molecular Docking to identify the antiviral metabolites and their mechanism of action if any. Linpinski’s rule of 5 and ADMET evaluation were used to screen drug like compounds and analyze pharmacokinetic properties. Our analysis revealed three ligands Cosmosiin (20), Baicalin (19) and Epicatechin-3-O-gallate (9) responsible for binding to target proteins with high affinity, where Cosmosiin (20) docked to Envelope gD, VP5, VP23, UL17 and UL36, Baicalin (19) interacted with Envelope gH-gL, VP19C, VP26 and Serine protease, and Epicatechin-3-O-gallate (9) docked to UL25. ADMET analysis showed optimum results except for a few parameters. Comparison of protein-ligand interactions with those reported earlier, enabled us to identify whether ligands were blocking the amino acids needed to interact with other molecules and complete lifecycle. The most promising results obtained for this examination were of CVSC, particularly of Cosmosiin (20) against UL17. Hence, we conclude that Polygonum aviculare has anti-HSV activity and propose three lead compounds as candidate drugs for further investigations. Since Cosmosiin (20) has not previously been reported for its anti-HSV-2 potential, we are the first ones to propose it as a novel antiviral agent. This is the first time C-capsid has been analyzed as a potential target for therapeutic intervention, opening avenues for new class of antivirals against HSV-2.