Determination of the G Protein of Nipah Virus and Its Ligands as a Potential New Anti-Nipah Viral Drug

Abstract

The aim of this study was to determine the full-length 3D structure of the Glyco (G) protein of Nipah virus, followed by the De Novo drug design, which will generate ligands as prospective Nipah virus inhibitor. Due to the unavailability of the complete structure of the Nipah virus in RCSB-PDB, Homology modelling was adopted by using the sequence from Uni Prot KB. BLAST assisted in the search of templates with the highest sequence similarity and coverage. After the joining of loops with the functional domains through ab-initio modelling, the full sequence of the Glyco (G) protein of Nipah virus was submitted in the i-TASSER server, which further predicted five models. Ramachandran assessment helped in the validation of those models. From the i- TASSER model, joining of the loops with the functional domains were cut off using UCSFChimera software. These loops and fragments were joined with the help of a tool that is in house developed. Once energy minimization has been carried out in the Swiss PDB viewer, CASTp server provided the determination of ligand binding pockets. After pocket determination, e- LEA3D server helped in the design of ligand molecules that will bind to those pockets. The pharmacokinetic properties of each of those ligands were further assessed in the Mobyle@RPBS web portal so that prospective Nipah virus inhibitor drugs can be developed in future.