The global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, has resulted in a negative impact on human health and on social and economic activities worldwide. Researchers around the globe need to design and develop successful therapeutics as well as vaccines against the novel COVID-19 disease. In the present study, we conducted comprehensive computer-assisted analysis on the spike glycoprotein of SARS-CoV-2 in order to design a safe and potent multiepitope vaccine. In silico epitope prioritization shortlisted six HLA I epitopes and six B-cell-derived HLA II epitopes. These high-ranked epitopes were all connected to each other via flexible GPGPG linkers, and at the N-terminus side, the sequence of Cholera Toxin β subunit was attached via an EAAAK linker. Structural modeling of the vaccine was performed, and molecular docking analysis strongly suggested a positive association of a multiepitope vaccine with Toll-like Receptor 3. The structural investigations of the vaccine-TLR3 complex revealed the formation of fifteen interchain hydrogen bonds, thus validating its integrity and stability. Moreover, it was found that this interaction was thermodynamically feasible. In conclusion, our data supports the proposition that a multiepitope vaccine will provide protective immunity against COVID-19. However, further in vivo and in vitro experiments are needed to validate the immunogenicity and safety of the candidate vaccine.

中文翻译：

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基于SARS-CoV-2穗状蛋白的针对COVID-19的多表位亚单位疫苗设计：计算机分析

由严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）（COVID-19的致病因子）引起的全球健康危机已对人类健康以及全球的社会和经济活动造成了负面影响。全球研究人员需要设计和开发成功的疗法以及针对新型COVID-19疾病的疫苗。在本研究中，我们对SARS-CoV-2的突触糖蛋白进行了全面的计算机辅助分析，以设计一种安全有效的多表位疫苗。在计算机电子表位中，优先排序列出了六个HLA I表位和六个B细胞衍生HLA II表位。这些高等级的表位都通过柔性GPGPG接头彼此连接，在N端侧，霍乱毒素β的序列亚基通过EAAAK接头连接。进行了疫苗的结构建模，并且分子对接分析强烈暗示了多表位疫苗与Toll样受体3呈正相关。疫苗-TLR3复合物的结构研究揭示了15个链间氢键的形成，从而验证了其完整性和稳定性。此外，发现这种相互作用在热力学上是可行的。总之，我们的数据支持以下观点：多表位疫苗将提供针对COVID-19的保护性免疫。但是，需要进一步的体内和体外实验来验证候选疫苗的免疫原性和安全性。