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AbstractSingle stranded RNA viruses were known to cause variety of diseases since many years and are gaining much importance due to pandemic after the identification of a novel corona virus (severe acute respiratory syndrome-coronavirus (SARS-CoV-2)). Seven coronaviruses (CoVs) are known to infect humans and they are OC43 CoV, NL63 CoV, HKU1 CoV, Middle East respiratory syndrome, SARS CoV, and SARS CoV-2. Virus replication weakens the immune system of host thereby altering T-cell count and much of interferon response. Although no vaccine or therapeutic treatment has been approved till now for CoV infection, trials of vaccine against SARS CoV-2 are in progress. One of the epitopes used for vaccine production is of the spike protein on the surface of virus. The work focuses on designing of multi-epitope vaccine construct for treatment of seven human CoV infections using the epitopes present on the spike protein of human CoVs. To address this, immuno-informatics techniques have been employed to design multi-epitope vaccine construct. B- and T-cell epitopes of the spike proteins have been predicted and designed into a multi-epitope vaccine construct. The tertiary structure of the vaccine construct along with the adjuvant has been modelled and the physiochemical properties have been predicted. The multi-epitope vaccine construct has antigenic and non-allergenic property. After validation, refinement and disulphide engineering of the vaccine construct, molecular docking with toll-like receptors (TLRs) have been performed. Molecular dynamics simulation in aqueous environment predicted that the vaccine-TLRs complexes were stable. The vaccine construct is predicted to be able to trigger primary immune response in silico. Communicated by Ramaswamy H. Sarma