Dengue viral disease has been reported as an Aedes aegypti mosquito-borne human disease and causing a severe global public health concern. In this study, immunoinformatics methods was deployed for crafting CTL T-cell epitopes as dengue vaccine candidates. The NS1 protein sequence of dengue serotype 1 strain retrieved from the protein database and T-cell epitopes (n = 85) were predicted by the artificial neural network. The conserved epitopes (n = 10) were predicted and selected for intensive computational analysis. The machine learning technique and quantitative matrix-based toxicity analysis assured nontoxic peptide selection. Hidden Markov Model derived Structural Alphabet (SA) based algorithm predicted the 3D molecular structure and all-atom structure of peptide ligand validated by Ramachandran-plot. Three-tier molecular docking approaches were used to predictthe peptide - HLA docking complex. Molecular dynamics (MD) simulation study confirmed the docking complex was stable in the time frame of 100ns. Population coverage analysis predicted the interaction epitope interaction with a particular population of HLA. These results concluded that the computationally designed HTLWSNGVL and FTTNIWLKL epitope peptides could be used as putative agents for the multi CTL T cell epitope vaccine. The vaccine protein sequence expression and translation were analyzed in the prokaryotic vector adapted by codon usage. Such in silico formulated CTL T-cell-based prophylactic vaccines could encourage the commercial development of dengue vaccines.
Keywords: Dengue; Docking; Epitope; Population coverage; Simulation; Vaccine.
Copyright © 2020. Published by Elsevier Ltd.