Multi-epitope vaccine against SARS-CoV-2 applying immunoinformatics and molecular dynamics simulation approaches

Abstract

COVID-19, caused by SARS-CoV-2, is severe respiratory illnesses leading to millions of deaths worldwide in very short span. The high case fatality rate and the lack of medical counter measures emphasize for an urgent quest to develop safe and effective vaccine. Receptor-binding domain (RBD) of spike protein of SARS-CoV-2 binds to the ACE2 receptor on human host cell for the viral attachment and entry, hence considered as a key target to develop vaccines, antibodies and therapeutics. In this study, immunoinformatics approach was employed to design a novel multi-epitope vaccine using RBD of SARS-CoV-2 spike protein. The potential B- and T-cell epitopes were selected from RBD sequence using various bioinformatics tools to design the vaccine construct. The in silico designed multi-epitope vaccine encompasses 146 amino acids with an adjuvant (human beta-defensin-2), which was further computationally evaluated for several parameters including antigenicity, allergenicity and stability. Subsequently, three-dimensional structure of vaccine construct was modelled and then docked with various toll-like receptors. Molecular dynamics (MD) study of docked TLR3-vaccine complex delineated it to be highly stable during simulation time and the stabilization of interaction was majorly contributed by electrostatic energy. The docked complex also showed low deformation and increased rigidity in motion of residues during dynamics. Furthermore, in silico cloning of the multi-epitope vaccine was carried out to generate the plasmid construct for expression in a bacterial system. Altogether, our study suggests that the designed vaccine candidate containing RBD region could provide the specific humoral and cell-mediated immune responses against SARS-CoV-2. Communicated by Ramaswamy H. Sarma