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基于蛋白质组学的循环 SARS-CoV-2 变体分析:迈向通用疫苗候选物的方法。

Proteome based analysis of circulating SARS-CoV-2 variants: approach to a universal vaccine candidate.

机构信息

Department of Microbiology, Laboratory of Molecular Biology, Immunology and Informatics, Adeleke University, Ede, Osun State, Nigeria.

Genomics Unit, Helix Biogen Institute, Ogbomoso, Oyo State, Nigeria.

出版信息

Genes Genomics. 2023 Dec;45(12):1489-1508. doi: 10.1007/s13258-023-01426-1. Epub 2023 Aug 7.

DOI:10.1007/s13258-023-01426-1
PMID:37548884
Abstract

The discovery of the first infectious variant in Wuhan, China, in December 2019, has posed concerns over global health due to the spread of COVID-19 and subsequent variants. While the majority of patients experience flu-like symptoms such as cold and fever, a small percentage, particularly those with compromised immune systems, progress from mild illness to fatality. COVID-19 is caused by a RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach involved utilizing immunoinformatic to identify vaccine candidates with multiple epitopes and ligand-binding regions in reported SARS-CoV-2 variants. Through analysis of the spike glycoprotein, we identified dominant epitopes for T-cells and B-cells, resulting in a vaccine construct containing two helper T-cell epitopes, six cytotoxic T-cell epitopes, and four linear B-cell epitopes. Prior to conjugation with adjuvants and linkers, all epitopes were evaluated for antigenicity, toxicity, and allergenicity. Additionally, we assessed the vaccine Toll-Like Receptors complex (2, 3, and 4). The vaccine construct demonstrated antigenicity, non-toxicity, and non-allergenicity, thereby enabling the host to generate antibodies with favorable physicochemical characteristics. Furthermore, the 3D structure of the B-cell construct exhibited a ProSA-web z-score plot with a value of -1.71, indicating the reliability of the designed structure. The Ramachandran plot analysis revealed that 99.6% of the amino acid residues in the vaccine subunit were located in the high favored observation region, further establishing its strong candidacy as a vaccination option.

摘要

2019 年 12 月在中国武汉发现的首个传染性变异株引发了全球对健康的担忧,原因是 COVID-19 的传播和随后的变异。虽然大多数患者出现类似流感的症状,如感冒和发烧,但一小部分患者,特别是免疫系统受损的患者,病情从轻度进展为致命。COVID-19 是由一种称为严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的 RNA 病毒引起的。我们的方法涉及利用免疫信息学来识别报告的 SARS-CoV-2 变异体中具有多个表位和配体结合区域的疫苗候选物。通过对刺突糖蛋白进行分析,我们确定了 T 细胞和 B 细胞的优势表位,从而产生了一种含有两个辅助 T 细胞表位、六个细胞毒性 T 细胞表位和四个线性 B 细胞表位的疫苗构建体。在与佐剂和接头缀合之前,所有表位都进行了抗原性、毒性和过敏性评估。此外,我们还评估了疫苗 Toll-Like Receptors 复合物(2、3 和 4)。疫苗构建体表现出抗原性、非毒性和非过敏性,从而使宿主能够产生具有良好物理化学特性的抗体。此外,B 细胞构建体的 3D 结构显示 ProSA-web z 得分图的数值为-1.71,表明设计结构的可靠性。Ramachandran 图分析显示,疫苗亚单位中 99.6%的氨基酸残基位于高置信观察区,进一步确立了其作为疫苗选择的强候选地位。

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