In-silico Discovery of Potential Dengue Type 2 Virus NS1 Inhibitors: A Natural Ligand Zingerone-Derived 3-Point Pharmacophore Screening and Structure-Guided Blind Docking Study

Abstract

This research endeavors to identify potential therapeutic candidates counter to DENV-2 NS1 through a computational approach. Utilizing the three-dimensional crystal structure of DENV-2 NS1 (PDB ID: 1OKE) as a molecular target, we employed a multi-step methodology involving ligand preparation, pharmacophore-based screening, and molecular docking simulations. Zingerone, a bioactive compound, served as the lead molecule for pharmacophore generation. Subsequently, a diverse set of compounds from the ChEMBL drug database was screened, and the top candidates were subjected to molecular docking studies. Noteworthy compounds, such as CHEMBL408701 (Taurolithocholic Acid) and CHEMBL4297253 (Mipicoledine), exhibited promising pharmacophore scores and binding interactions within specific pockets of DENV-2 NS1. Future drug development efforts against dengue virus infections can be built upon the study’s foundation, highlighting these compounds’ potential as inhibitors.