Molecular docking and simulation studies towards exploring antiviral compounds against envelope protein of Japanese encephalitis virus

Abstract

Japanese encephalitis (JE) is an acute central nervous system inflammatory disease caused by the Japanese encephalitis virus (JEV). JEV is a small, enveloped, plus-strand RNA virus belonging to the genus Flavivirus. In this study, envelope protein (E) that mediates the entry of JEV into host cell has been preferred as potential molecular target for drug development. The 3-D structure of E protein was designed and validated using modeler9.10 and procheck tool, respectively, and also optimized using molecular dynamics simulation. A number of lead molecules were used for computational virtual screening against JEV E protein. Three top ranked lead molecules with strong binding affinity to JEV E protein were identified based on minimum binding energy. Molecular dynamic simulation was also performed for protein-ligand complex to study the mobility of complex at various time intervals. Drug likeliness and comparative bioactivity analysis for these leads using OSIRIS Property Explorer had shown that these molecules would have the potential to act as better drug. The mycophenolate was found to be most suitable as entry inhibitor therapeutic molecule for JEV E protein, which may be considered as a potential ligand for treatment of Japanese encephalitis. © 2013 Springer-Verlag Wien.