Inhibition studies of methyltransferase domain of dengue virus protein NS-5 by a poly herbal extract- An Insilico Apporach.

Abstract

Dengue is a mosquito borne viral disease mainly transmitted by Aedes aegypti and, to a lesser extent, Ae. albopictus. The global incidence of Dengue is grown dramatically in recent decades. Dengue is endemic in over 100 countries and there are an estimated 100-400 million infections every year. Currently no antiviral drugs are available against Dengue. This urges a strong need to develop therapeutic strategies that can tackle this life threatening disease. In this study, the efficiency of nine bioactive chemical entities from Nilavembu Kudineer, a popularly known traditional Siddha formulation have been analyzed for their in silico docking potentials against NS-5 methyltransferase of Dengue virus. Methyltransferase is responsible for capping the nascent genomic RNA of Dengue Virus, using S-Adenosyl methionine as a methyl group donar, this methylation of viral RNA plays a major role allowing the virus to escape the immune response. A graphical automated drug discovery system called iGEMDOCK is used for integrating docking, screening, post analysis and visualization. Current investigation clearly focuses on pharmacological interactions of polyherbal drug in preventing the capping of mRNA, thereby inhibiting RNA dependent RNA polymerase (RdRp), ultimately hindering the post transcriptional modifications. Out of the nine ligands screened for its antiviral activity, Monolinolein and Palmitic acid showed binding energies >90 Kcal/mol towards the binding site of NS-5 methyltransferase and could be the active pharmaceutical ingredients of Nilavembu kudineer.