Journal of biomolecular structure & dynamics · 2019
Design of novel multi-epitope vaccines against severe acute respiratory syndrome validated through multistage molecular interaction and dynamics.
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Srivastava Sukrit, Kamthania Mohit, Kumar Pandey Rajesh, Kumar Saxena Ajay, Saxena Vaishali, Kumar Singh Santosh, Kumar Sharma Rakesh, Sharma Nishi
Аннотация
Severe acute respiratory syndrome (SARS) is endemic in South China and is continuing to spread worldwide since the 2003 outbreak, affecting human population of 37 countries till present. SARS is caused by the severe acute respiratory syndrome Coronavirus (SARS-CoV). In the present study, we have designed two multi-epitope vaccines (MEVs) composed of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B cell epitopes overlap, bearing the potential to elicit cellular as well as humoral immune response. We have used truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 as molecular adjuvants at N-terminal of both the MEVs. Selected overlapping epitopes of both the MEVs were further validated for stable molecular interactions with their respective human leukocyte antigen class I and II allele binders. Moreover, CTL epitopes were further studied for their molecular interaction with transporter associated with antigen processing. Furthermore, after tertiary structure modelling, both the MEVs were validated for their stable molecular interaction with Toll-like receptors 2 and 4. Codon-optimized cDNA of both the MEVs was analysed for their potential high level of expression in the mammalian cell line (Human) needed for their further in vivo testing. Overall, the present study proposes in silico validated design of two MEVs against SARS composed of specific epitopes with the potential to cause a high level of SARS-CoV specific cellular as well as humoral immune response. Communicated by Ramaswamy H. Sarma.
Предметные рубрики MeSH
ATP-Binding Cassette TransportersAnimalsCell LineEpitopes, B-LymphocyteEpitopes, T-LymphocyteHLA AntigensHumansMolecular Docking SimulationMolecular Dynamics SimulationOnchocerca volvulusSevere acute respiratory syndrome-related coronavirusSevere Acute Respiratory SyndromeT-Lymphocytes, CytotoxicT-Lymphocytes, Helper-InducerToll-Like Receptor 2Toll-Like Receptor 4Viral Envelope ProteinsViral Vaccines