Harnessing the Power of Bioinformatics Pipelines to Develop an Anti-SARS-CoV-2 Pan-Species Vaccine: A Post-Pandemic Description

Background: The emergence of infectious agents enforces rapid prophylactic/therapeutic development. Accordingly, multi-epitope vaccines represent a milestone in the second-generation vaccines to break the SARS-CoV-2 transmission chain, a zoonotic virus, and decrease long coronavirus (COVID-19) complications. Thus, this study aimed to present a potent anti-SARS-CoV-2 pan-species vaccine candidate via computational workflow to address this hypothesis: Could a multi-epitope construct provoke effective anti-SARS-CoV-2 protection as a bioinformatics solution? Methods: The B-cell and T-cell epitopes of the S1 domain, N, Nsp4, Nsp12, and ORF6 proteins were predicted regarding the significant role of viral proteins in the infection cycle. Then, the final construct was designed as (1) scaffolding by the top-ranked epitopes, β-defensin, His6-tag, (2) structural modeling/refinement, (3) molecular docking/dynamics simulation, and (4) validation. Results: The 15 linear B-cell, 7 helper T-cell, and 11 cytotoxic T-cell epitopes were embedded within the construct, all located outside the hyper-variable regions of target proteins. Following the quality assessment, its best binding affinity was observed with TLR4, TLR8, HLA-DRB1*01:01, HLA-A*03:01, and ACE2. The strong interactions were also observed with a validated single-chain variable fragment as a preliminary in silico indication about its possible in vivo efficiency. Moreover, the messenger RNA stability and robust immune stimulation were verified. Not only was non-significant homology found between the multi-epitope vaccine construct and some viral hosts/reservoir proteomes, but also significant coverage was detected between human immune receptors and their counterparts in domestic, wildlife, and captive animals. Therefore, it could be a sign of the possible efficiency of the construct as a pan-species vaccine. Conclusion: Despite the end of the COVID-19 pandemic, a combinatorial workflow was introduced to design a vaccine with potential application in various species, whereas many other studies have not employed all of these criteria, and according to our information, this is one of the few works to introduce such constructs.