The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8⁺ and Three CD4⁺ T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.

中文翻译：

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靶向SARS-CoV-2核蛋白磷酸蛋白RNA结合域的减毒亚组分疫苗设计：计算机分析。

严重的急性呼吸系统综合症冠状病毒2（SARS-CoV-2）引起的新型冠状病毒疾病（COVID-19）以前从未被人类发现，从而在公共卫生领域造成毁灭性打击。对于抑制这种流行病的有效疫苗的需求不能过分强调。有鉴于此，我们设计了一种靶向核衣壳蛋白的N端（NT）和C端（CT）RNA结合域的亚组分抗原肽疫苗，该疫苗有助于病毒复制。有前景的抗原性B细胞和T细胞抗原决定簇使用计算管道进行了预测。肽“ RIRGGDGKMKMDL”和“ AFGRRGPEQTQGNFG”是具有良好抗原指数和非过敏特性的B细胞线性表位。两张CD8 ⁺和三张CD4 ⁺还应考虑到T细胞表位的安全性，例如变应原性，抗原水平保守性，抗原性，肽毒性以及对MHC-I和MHC-II等位基因的假定限制，来选择T细胞表位。利用这些选择的表位，构建了不能诱导II型超敏反应的非过敏性嵌合肽疫苗。通过分子对接分析了疫苗触发的Toll样受体5（TLR5）之间的分子相互作用，并使用动力学模拟对其进行了详细研究。最后，利用pET-28a载体进行计算机克隆以确保疫苗的表达和翻译效率。因此，这项研究为实验研究和验证提供了指南。