A novel infectious agent, SARS-CoV-2, is responsible for causing the severe respiratory disease
COVID-19 and death in humans. Spike
glycoprotein plays a key role in viral particles entering host cells, mediating receptor recognition and membrane fusion, and are considered useful targets for
antiviral vaccine candidates. Therefore, computational techniques can be used to design a safe, antigenic, immunogenic, and stable
vaccine against this pathogen. Drawing upon the structure of the S
glycoprotein, we are trying to develop a potent multi-
epitope subunit vaccine against SARS-CoV-2. The
vaccine was designed based on cytotoxic T-lymphocyte and helper T-lymphocyte
epitopes with an N-terminal adjuvant via conducting immune filters and an extensive immunoinformatic investigation. The safety and immunogenicity of the designed
vaccine were further evaluated via using various physicochemical, allergenic, and antigenic characteristics.
Vaccine-target (
toll-like receptors: TLR2 and TLR4) interactions, binding affinities, and dynamical stabilities were inspected through molecular docking and molecular dynamic (MD) simulation methods. Moreover, MD simulations for dimeric TLRs/
vaccine in the membrane-aqueous environment were performed to understand the differential domain organization of TLRs/
vaccine. Further, dynamical behaviors of
vaccine/TLR systems were inspected via identifying the key residues (named HUB nodes) that control interaction stability and provide a clear molecular mechanism. The obtained results from molecular docking and MD simulation revealed a strong and stable interaction between
vaccine and TLRs. The
vaccine's ability to stimulate the immune response was assessed by using computational immune simulation. This predicted a significant level of cytotoxic T cell and helper T cell activation, as well as
IgG,
interleukin 2, and
interferon-gamma production. This study shows that the designed
vaccine is structurally and dynamically stable and can trigger an effective immune response against
viral infections.