Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: an in silico approach

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19), a public health emergency of international concerns declared by the World Health Organization (WHO). An immuno-informatics approach along with comparative genomics was applied to design a multi-epitope-based peptide vaccine against SARS-CoV-2 combining the antigenic epitopes of the S, M, and E proteins. The tertiary structure was predicted, refined and validated using advanced bioinformatics tools. The candidate vaccine showed an average of ≥90.0% world population coverage for different ethnic groups. Molecular docking and dynamics simulation of the chimeric vaccine with the immune receptors (TLR3 and TLR4) predicted efficient binding. Immune simulation predicted significant primary immune response with increased IgM and secondary immune response with high levels of both IgG1 and IgG2. It also increased the proliferation of T-helper cells and cytotoxic T-cells along with the increased IFN-γ and IL-2 cytokines. The codon optimization and mRNA secondary structure prediction revealed that the chimera is suitable for high-level expression and cloning. Overall, the constructed recombinant chimeric vaccine candidate demonstrated significant potential and can be considered for clinical validation to fight against this global threat, COVID-19.

COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation

“…Although this was designed, and multiple amino acids from the 3 epitopes in the NOM protein are contributing to the binding to TLR4, it shows that components of SARS-COV-2 are binding well to TLR4 and raises further questions. More recently, several other in silico studies have designed multiepitope vaccines using SARS-CoV-2 spike glycoprotein constructs/subunits, and they are found to bind TLR4 using molecular docking studies (see [ 115 – 119 ]).…”

Evolutionary Analysis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reveals Genomic Divergence with Implications for Universal Vaccine Efficacy

“…In order to find out the impact of identified mutations and their implications on vaccine development, we have investigated the reported vaccine candidates from previous studies [ 51 , 52 , 53 , 54 , 55 , 56 ]. The identified mutations in the structural proteins were mapped with these vaccine candidates and it was found that 23 mutations in S protein, 1 in E, 2 from M, and 7 from N protein were observed to map with the reported B-cell and T-cell epitopes ( Supplementary File S9 ).…”

Immunoinformatic design of a COVID-19 subunit vaccine using entire structural immunogenic epitopes of SARS-CoV-2

“…Antigenic properties of spike glycoprotein were more focused by theory and experimental researchers [20][21][22] . Applying this basic knowledge, a number of peptide-based designs have been presented to date, which encompass those integrating epitopes from a single or few viral protein(s) [23][24][25][26][27] to those considering the whole proteome of the virus 28 . The present research contributes to current understanding in this field by offering an alternative approach for developing a potential COVID-19 vaccine, where the entire set of structural proteins were searched for most efficacious epitopic segments.…”

“…Triggering TLR-3 may help induce the TLR signalling networks which activate the immune pathways evolved specifically against viral pathogens. In addition, this TLR choice was a consensus from vaccine design research works on viral/retroviral pathogens, specifically coronavirus species 12 , 14 , 25 , 26 , 42 , 43 . While we note that other Toll-like immune receptors such as TLR-2, -4, -5, -7 and -8 may be stimulated by the COVID-19 virus, they were not considered here as their exact roles are not established, with some possibly functioning even to the advantage of the coronavirus 44 , 45 .…”