Identification of novel inhibitor against dengue NS5

Abstract

Dengue fever, a neglected emerging disease for which no vaccine or antiviral agents exist at present, is caused by dengue virus, a member of the Flavivirus genus, which includes several important human pathogens, such as yellow fever and West Nile viruses. The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S -adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. In this scenario, the present study aims to identify new molecules which could block or suppress the activity of RNA dependent RNA polymerase enzyme by molecular docking studies using Autodock Vina. In this study we used in silico approach by modeling NS5 protein, Optimization of the structure was done by adding polar hydrogens and Kollman charges using Pyrx .We further carried out docking studies by means of Autodock Vina, with various phytochemicals. Based on binding energy, phytochemicals were screeened and their interaction with NS5 was identified. Thus, we report Rohitukine alkaloid that has successfully satisfied all in silico parameters, necessitating further in vitro and in vivo studies. The improved conditions and new structural information should accelerate structure-based design of antiviral compounds against Dengue virus.