Sunil Kumar Gupta
Bioinformatics Centre, India
Posters & Accepted Abstracts: Virol-mycol
Flavivirus encephalitis is an acute central nervous system inflammatory disease generally causes by the Japanese Encephalitis Virus (JEV), West Nile virus (WNV) St. Louis encephalitis virus (STEV), Murray Valley encephalitis virus (MVEV) and Tick-borne encephalitis virus (TBEV) belonging to genus Flavivirus (family Flaviviridae). Over 100 countries throughout the world, more than 2.5 billion people are at risk of infection and around 20 million infections are annually reported. In the present study, NS3 protein of Flavivirus encephalitis has been preferred as probable molecular target for drug development. Flavivirus encephalitis NS3 protein is a large multifunctional protein plays an essential role in the Flavivirus life cycle. The NS3 N-terminal protease (NS3pro) simultaneously with its critical cofactor NS2B is involved in proteolytic processing of the viral poly protein, whereas the C-terminal NTPase/helicase is responsible for RNA replication. The three dimensional (3D) structure of all NS3 proteins of Flavivirus encephalitis were designed and validated using modeler 9.12 and PROCHECK tool, respectively and also optimized using molecular dynamics simulation. Mutation analysis and amino acid residues associated in active pocket have been analyzed. About 17588 lead molecules were used for computational virtual screening against NS3 protein and finally 361 lead molecules were found appropriate for docking study. Five top ranked lead molecules with strong binding affinity to all NS3 proteins were identified based on minimum binding energy. Molecular dynamic simulation was also performed for protein-ligand complex which have minimum binding energy, to study the mobility of complex at various time intervals. Drug likeliness, comparative bioactivity and other biochemical properties of lead molecules were recognized using OSIRIS Property Explorer. As result of the study 4-Epi Minocycline (CID 54687237) was found suitable as viral replication inhibitor therapeutic molecule for Flavivirus Encephalitis, which may be considered as a potential ligand for treatment of Flavivirus Encephalitis. Such studies may contribute to new approaches to antiviral drug development against Encephalitis.