In silico Characterization of NS4A and NS4B in DENV4
Student name: Mr Abhimanyu Singh
Guide: Dr Chaithanya Madhurantakam
Year of completion: 2018
Host Organisation: TERI School of Advanced Studies
Abstract: NS4A and NS4B are the family of proteins found in the flaviviruses which play a crucial role in the life cycle of virus. Dengue viral serotypes(1 to4) studies have indicated that NS4A helps in viral replication whereas NS4B is implicated in viral pathogenesis. The in-silico characterization studies of NS4A and NS4B includes identification of structural homologs with maximum sequence similarity, recognition of conserved amino acid residues in serotypes DENV1 to DENV4 as well as their evolutionary relationships. Along with other non-structural proteins, NS4A and NS4B proteins play a key role in viral replication in host organism. To successfully complete the life cycle in host cell, it is necessary that the Dengue virus evades host cell’s innate immune response. One of the several mechanisms adopted by the host is RNAi (RNA interference) and the Dengue virus developed a strategy wherein, the virus particles inhibit the synthesis of siRNAs (small interfering RNAs) specifically, through the inactivation of the dicer molecule that is necessary for the synthesis of siRNA. Dicer has been observed to interact with TRBP, a TAR Binding Protein. Therefore, studying the interaction between NS4B and dicer and identifying the active site residues between them help in identification ofcertain ligand molecules which can prevent such interaction inhibiting RNAi suppression and in turn reducing the chances of survival of virus within the host cell.
Keywords- NS4A and NS4B, Structure prediction, RNAi suppression, Dicer Chain A, Molecular Docking
