Proteome Exploration of human coronaviruses for Identifying Novel vaccine candidate: A Hierarchical Subtractive Genomics and Reverse Vaccinology Approach.

BACKGROUND: The SARSCoV-2 is responsible for infecting more than 271,000,000 people in 222 countries by December 10, of which 5,300,000 have died. COVID-19 was introduced by World Health Organization as a global concern and a pandemic disease due to the prevalence of disease. OBJECTIVES: Developing of preventive or therapeutics medication against novel-cov2019 is an urgent need, and has high priority among scientific societies, in this regard, the production of effective vaccines is one of the most significant and high-priority necessity. To date specific antiviral therapeutic and prophylactic vaccine for novel coronavirus (n-CoV2019) are not available. Because of costing and time-consuming of experimental strategies during vaccine design procedure, different immunoinformatics methods were developed. Recently Because of defect study on proteins of n-cov2019, its recommended to study other human coronaviruses. METHODS: At the beginning of vaccine design, the proteome study is essential. In this investigation, the whole human coronaviruses proteome was evaluated using proteome subtraction strategy. Out of 5945 human coronavirus proteins, five new antigenic proteins were selected by analyzing the hierarchical proteome subtraction and then their various physicochemical and immunological properties were also investigated bioinformatically. RESULTS: All five protein sequences are antigenic and non-allergenic proteins; moreover, spike protein group including Spike glycoprotein (E2) (Peplomer protein), spike fragment and spike glycoprotein fragment showed acceptable stability, which can be used to design new vaccines against human coronaviruses. CONCLUSION: These selected peptides and the other introduced protein in this study (HE, orf7a, SARS_X4 domain-containing protein and protein 8) can be employed as a suitable candidate for developing novel prophylactic or therapeutic vaccine against human coronaviruses.

Hotspots for mutations in the SARS-CoV-2 spike glycoprotein: a correspondence analysis.

Spike glycoprotein (Sgp) is liable for binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the host receptors. Since Sgp is the main target for vaccine and drug designing, elucidating its mutation pattern could help in this regard. This study is aimed at investigating the correspondence of specific residues to the SgpSARS-CoV-2 functionality by explorative interpretation of sequence alignments. Centrality analysis of the Sgp dissects the importance of these residues in the interaction network of the RBD-ACE2 (receptor-binding domain) complex and furin cleavage site. Correspondence of RBD to threonine500 and asparagine501 and furin cleavage site to glutamine675, glutamine677, threonine678, and alanine684 was observed; all residues are exactly located at the interaction interfaces. The harmonious location of residues dictates the RBD binding property and the flexibility, hydrophobicity, and accessibility of the furin cleavage site. These species-specific residues can be assumed as real targets of evolution, while other substitutions tend to support them. Moreover, all these residues are parts of experimentally identified epitopes. Therefore, their substitution may affect vaccine efficacy. Higher rate of RBD maintenance than furin cleavage site was predicted. The accumulation of substitutions reinforces the probability of the multi-host circulation of the virus and emphasizes the enduring evolutionary events.