Informatics in Medicine Unlocked (Jan 2021)
Exploring E, NS3, and NS5 proteins to design a novel multi-epitope vaccine candidate against West Nile Virus: An in-silico approach
Abstract
West Nile Virus is a spherical, enveloped capsid with a single-stranded RNA molecule and a known pathogen responsible for encephalitis. The deficiency of adequate treatment for WNV resulted in an increased mortality rate in its endemic zones, consequently causing its emergence as a primary health concern on both national and international scales as brain inflammation/infections caused by WNV are proved to be lethal. Thus, potential vaccination against WNV is the most viable candidate for remediation. A multi-epitope prophylactic/therapeutic vaccine targeting the pathogen's major structural and functional infective proteins (E, NS3, and NS5 proteins in this study) would be invaluable to achieve the current elimination goal. The present study was conducted with the directive to design a chimeric epitope-based vaccine exploiting immunoinformatics methods. After a thorough investigation, a plausible candidate was selected with the combination of twelve T-cell epitopes and nine B-cell epitopes along with appropriate adjuvant and linkers. Physicochemical features were analyzed, and the tertiary structure of the vaccine candidate was predicted, refined, and validated. Further molecular docking study revealed significant results of solid binding interactions of the vaccine with its specific receptor. The molecular dynamics results showed the complex rigidity, a low deformation index, and stable binding between the vaccine and the receptor with small atomic fluctuations, thus considering the vaccine as a potential candidate. Furthermore, an immune simulation was also performed to observe the immunological responses upon administration into humans, which evaluate the efficiency of the vaccine construct to derive robust immune responses like increased level of T-cells, cytokines, and antibodies to combat against the virus. Finally, codon adaptation and in-silico cloning were accomplished to design an effective mass production strategy of the vaccine. This study implies that the predicted vaccine can be a potential candidate that must undergo wet-lab-based observations.
