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

Abstract

The primary objective of this study was to discover the major (P) protein of the Nipah virus's full-length 3D structure. This was done in preparation for a De Novo drug design that would provide potential Nipah virus inhibitor ligands. The Nipah virus' full structure was not included in the RCSB-PDB, thus homology modeling was used in conjunction with the Uni Prot KB sequence. The search for templates with the greatest sequence similarity and coverage was aided by BLAST. The whole sequence of the large (P) protein of the Nipah virus was entered into the i-TASSER server after loops and functional domains were joined by ab-initio modeling, which further predicted five models. The Ramachandran analysis was useful in validating such models. Using UCSF-Chimera software, the linking of the loops with the functional domains from the i-TASSER model was removed. With the use of a custom tool created in-house, these loops and pieces were connected. After the Swiss Pdb viewer server has completed its energy minimization, the CASTp server has delivered the identification of ligand binding pockets. Following the identification of the pockets, the e-LEA3D server assisted in creating the ligand molecules that would bind to those pockets. To facilitate the development of potential Nipah virus inhibitor medications in the future, the pharmacokinetic characteristics of each of those ligands were further evaluated on the Mobyle@RPBS website.