Abstract
The SARS-CoV-2 pandemic has created a public health crisis worldwide. Although vaccines against the virus are efficiently being rolled out, they are proving to be ineffective against certain emerging SARS-CoV-2 variants. The high degree of sequence similarity between SARS-CoV-2 and other human coronaviruses (HCoV) presents the opportunity for designing vaccines that may offer protection against SARS-CoV-2 and its emerging variants, with cross-protection against other HCoVs. In this study, we performed bioinformatics analyses to identify T and B cell epitopes originating from spike, membrane, nucleocapsid, and envelope protein sequences found to be evolutionarily conserved among seven major HCoVs. Evolutionary conservation of these epitopes indicates that they may have critical roles in viral fitness and are, therefore, unlikely to mutate during viral replication thus making such epitopes attractive candidates for a vaccine. Our designed vaccine construct comprises of twelve T and six B cell epitopes that are conserved among HCoVs. The vaccine is predicted to be soluble in water, stable, have a relatively long half-life, and exhibit low allergenicity and toxicity. Our docking results showed that the vaccine forms stable complex with toll-like receptor 4, while the immune simulations predicted that the vaccine may elicit strong IgG, IgM, and cytotoxic T cell responses. Therefore, from multiple perspectives, our multi-subunit vaccine design shows the potential to elicit a strong immune-protective response against SARS-CoV-2 and its emerging variants while carrying minimal risk for causing adverse effects.
Highlights
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide pandemic that continues to negatively impact the global economy, social dynamics, and health care systems [1]
In order to analyze the evolutionary relationship between SARS-CoV-2 with other human coronaviruses (HCoV) (SARS-CoV, MERS-CoV, HCoV-NL63, HCoV-229E, HCoV-OC43, and HKU-1), nucleotide alignment was used to construct a maximum-likelihood (ML) phylogenetic tree using IQ-TREE v1.6.12 [25]
The results revealed several regions within N, M, and S proteins exhibiting more than 40% homology among the seven HCoVs, while no conserved regions were found for the E protein (Supplementary Figure S3), corroborating the findings of the phylogenetic analysis
Summary
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide pandemic that continues to negatively impact the global economy, social dynamics, and health care systems [1]. SARS-CoV-2 has been identified as the seventh coronavirus that can infect humans [2]. Coronaviruses have infected the human population repeatedly over the past century [3], only a few have caused severe large-scale outbreaks. Prior to SARS-CoV-2, the SARS-CoV outbreak occurred in southern China in November 2002, followed by the Middle East respiratory syndrome (MERS-CoV) outbreak in Saudi Arabia and South Korea, respectively, in 2012 and 2015. Four other human coronaviruses (HCoVs) associated with mild upper respiratory symptoms, have previously been identified, i.e., HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoVHKU1 [6,7,8]
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