Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In Silico Analysis.

Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In Silico Analysis.
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DOI:
10.1155/2020/2837670
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发表时间:
2020
影响因子:
4.1
通讯作者:
Okinedo EU
Okinedo EU
中科院分区:
医学3区
文献类型:
--
作者:
Chukwudozie OS;Chukwuanukwu RC;Iroanya OO;Eze DM;Duru VC;Dele-Alimi TO;Kehinde BD;Bankole TT;Obi PC;Okinedo EU

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由严重急性呼吸道综合征冠状病毒2型(SARS-CoV-2)引起的新型冠状病毒疾病(COVID-19)以前从未在人类身上发现过,从而对公共卫生造成了破坏。需要一种有效的疫苗来遏制这一流行病,这一点怎么强调都不过分。鉴于此,我们设计了一种亚组分抗原肽疫苗,其靶向核衣壳蛋白的N-末端(NT)和C-末端(CT)RNA结合结构域,其有助于病毒复制。使用计算流水线预测有前景的抗原性B细胞和T细胞表位。“RIRGGDGKMKDL”和“AFGRRGPEQTQGNFG”为B细胞线性表位,具有良好的抗原性和非致敏性。还选择了两个CD 8+和三个CD 4 + T细胞表位,考虑到它们的安全免疫原性谱,如变应原性、抗原水平保护性、抗原性、肽毒性和对许多MHC-I和MHC-II等位基因的推定限制。利用这些选择的表位,构建了不能诱导II型超敏反应的非变应原性嵌合肽疫苗。通过分子对接和动力学模拟分析了疫苗诱导的Toll样受体5(TLR 5)之间的分子相互作用。最后,利用pET-28 a载体进行电子克隆以确保疫苗的表达和翻译效率。因此,本研究为实验研究和验证提供了指导。
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.
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