Application of in silico techniques and artificial intelligence for the design of a recombinant vaccine based on SARS CoV-۲

Background and aims: SARS CoV-۲ Infection is initiated by binding of spike protein to ACE۲receptor on host cell surface. Therefore, spike protein can be considered as a target for the developmentof a potential vaccine against COVID-۱۹. The aim of this study is to design in silico usingartificial intelligence and production of a recombinant vaccines against SARS CoV-۲.Method: To date, numerous studies have been conducted on SARS CoV-۲. Considering the importantrole of spike protein in SARS CoV-۲ infection, its sequence was obtained from the NCBIdatabase at https://www.ncbi.nlm.nih.gov/.The obtained sequence was used to perform a BLASTsearch at https://blast.ncbi.nlm.nih.gov/Blast.cgi. The PSI-BLAST (Position-Specific IteratedBLAST) tool of the protein BLAST was employed to find the highly similar protein sequences.Different parts of the spike sequence were investigated for their role in host cell entry of SARSCoV-۲, alongside its glycosylation regions, disulfide bonds and predicted epitopes. Important domainssuch as receptor binding domain (RBD), fusion peptide (FP), and cleavage site (CS), whichplayed key roles in the binding and fusion of the viral genome into the host cell, were selected.Then, the sequences that had the most suitable epitopic index were selected from these parts.The selected sequences were evaluated in regards to their expression limitations in prokaryotichosts (such as post-translational modifications), then the selection of such parts were disregarded.Furthermore, the selected sequences were analyzed in terms of their epigenetics, antigenicity,allergenicity, physicochemical properties, signal peptides, glycosylation sites, toxicity, disulfidebonds, primary structures, secondary structures and tertiary structures using in silico techniquesand different data bases .the Jcat tool at http://www.jcat.de/ was employed to optimize the DNAsequences for high levels of protein expression (the E. coli codon usage bias was used for the optimization).Following the final confirmation of the selected parts, the ۳D structure of the recombinantspike protein was predicted by the Robetta server whereas the ۳D structure of ACE۲ wasobtained RCSB, and they were applied to assess the binding capability of the recombinant spikeprotein to ACE۲ using the HDOCK server.Results: Bioinformatic studies showed that the selected protein sequence was proper for expressionin the prokaryotic system in terms of epigenetic and antigenic indicators and the absence ofpost-translation modifications, etc. furthermore, the results of intermolecular docking of designedprotein with ACE۲ receptor indicate a strong connection between ligand and receptor.Conclusion: According to the bioinformatic studies results, the recombinant protein designed tobe used in a vaccine has the potent potential to start in vitro studies. Considering the advantages ofproducing this type of vaccines (including: rapid growth rate, continuous fermentation capacity,low cost of culture medium, high expression level and lower risks compared to the productionof viral vaccines after it was confirmed in the laboratory stage, we conclude that it is a suitableoption for the production of recombinant vaccines against SARS CoV-۲