Comparative analysis of structural characteristics and epitopes in S proteins between SARS-CoV-2 and SARS-CoV

doi:10.3785/j.issn.1008-9292.2020.05.01

J Zhejiang Univ (Med Sci)

2020, Vol. 49

Issue (3): 315-323 DOI: 10.3785/j.issn.1008-9292.2020.05.01

Comparative analysis of structural characteristics and epitopes in S proteins between SARS-CoV-2 and SARS-CoV

LUN Yongzhi*(

),LIU Ben,DONG Wen,SUN Jie,PAN Linghong

Key Laboratory of Medical Microecology(Putian University), Fujian Province University, School of Pharmacy and Medical Technology, Putian University, Putian 351100, Fujian Province, China

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Abstract

Objective: To provide data support for the study of pathogenic mechanism of SARS-CoV-2 at the molecular level, and provide suitable candidate targets for vaccine, antibody and drug research and development through comparative analysis for structural characteristics and epitopes of S protein of SARS-CoV-2 and SARS-CoV. Methods: Based on the reference sequences of S protein, physical and chemical properties, hydrophobicity, signal peptide, transmembrane region, domain, secondary structure, tertiary structure analysis and antigenic epitopes prediction were carried out. Meanwhile, the tissue expression, related pathways and reactome pathways of angiotensis Ⅰ converting enzyme 2 (ACE2) and C-type lectin domain family 4 member M (CLEC4M) receptors were analyzed. Results: The amino acid sequence of S protein of SARS-CoV-2 and SARS-CoV has a 75.80% consistency. The structural characteristics of the two coronaviruses are highly consistent, but the secondary structure and tertiary structure of SARS-CoV-2 is not as obvious as SARS-CoV. ACE2 and CLEC4M are expressed in alimentary system, heart, kidney, lung and placenta. The main related the pathways of renin-angiotensin system, protein digestion and absorption pathway, and the reactome pathways of metabolism of angiotensinogen to angiotensins, GPCR ligand binding, are related to typical symptoms of coronavirus disease 2019 induced by SARS-CoV-2. Three pairs of highly or completely homologous epitopes of S protein were obtained. The 600-605, 695-703 and 888-896 amino acid residues in SARS-CoV-2 were highly homologous with 586-591, 677-685 and 870-878 amino acid residues in SARS-CoV, respectively. Conclusions: The similarity of S protein of SARS-CoV-2 and SARS-CoV determines that they have similar infection patterns and clinical manifestations. The candidate epitopes with high reliability can provide reference for virus diagnosis and vaccine development.

Key words： Severe acute respiratory syndrome coronavirus 2 S protein Structural characteristic Epitope

Received: 16 April 2020 Published: 10 June 2020

CLC:

R373.1

Corresponding Authors: LUN Yongzhi E-mail: lunyz@163.com

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Cite this article:

LUN Yongzhi,LIU Ben,DONG Wen,SUN Jie,PAN Linghong. Comparative analysis of structural characteristics and epitopes in S proteins between SARS-CoV-2 and SARS-CoV. J Zhejiang Univ (Med Sci), 2020, 49(3): 315-323.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.05.01 OR http://www.zjujournals.com/med/Y2020/V49/I3/315

两种严重急性呼吸综合征冠状病毒S蛋白结构特征及抗原表位比较

目的: 通过严重急性呼吸综合征冠状病毒（SARS-CoV）-2与SARS-CoV S蛋白结构特征及抗原表位的比较分析，从分子水平为SARS-CoV-2致病机制研究提供数据支持，并为疫苗、抗体及药物研发寻找合适的候选靶点。方法: 利用生物信息学方法和工具，基于S蛋白参考序列进行理化性质、疏水性、信号肽、跨膜区、结构域、二级结构、三级结构分析及抗原表位预测，同时对受体血管紧张素转换酶2（ACE2）、C型凝集素（CLEC4M）的组织表达及关联通路、途径进行分析。结果: SARS-CoV-2、SARS-CoV S蛋白氨基酸序列一致性为75.80%，两者结构特征具有较高一致性，但SARS-CoV-2高级结构特征不如SARS-CoV明显。受体ACE2、CLEC4M在消化系统及心脏、肾脏、肺、胎盘中均有表达，主要关联的肾素-血管紧张素系统、蛋白质消化吸收通路及血管紧张素前体转化、G蛋白偶联受体（GPCR）配体结合途径与2019冠状病毒病典型症状相关。分析获得S蛋白三对高度或完全同源的抗原表位，即SARS-CoV-2 S蛋白第600~605位氨基酸残基与SARS-CoV第586~591位高度一致，SARS-CoV-2 S蛋白第695~703位、第888~896位氨基酸残基分别与SARS-CoV第677~685位、第870~878位高度或完全一致。结论: SARS-CoV-2与SARS-CoV S蛋白结构上的相似性决定了两者具有相近的感染模式和临床表现。筛选获得的高可信度的SARS-CoV-2候选抗原表位可为病毒诊断和疫苗研制提供参考。

关键词： 严重急性呼吸综合征冠状病毒2, S蛋白, 结构特征, 抗原表位

Tab 1 Physicochemical properties of S protein in SARS-CoV-2 and SARS-CoV

Fig 1 Hydrophobicity of S protein in SARS-CoV-2 and SARS-CoV

Tab 2 Structural functional domain of S protein in SARS-CoV-2 and SARS-CoV

Fig 2 Structural features of the amino acid sequence of S protein in SARS-CoV-2 and SARS-CoV

Fig 3 Tertiary structure of S protein in SARS-CoV-2 and SARS-CoV

Fig 4 Multiple alignment of the amino acid sequences of S protein in SARS-CoV-2 and SARS-CoV

Fig 5 Expression level of receptor proteins ACE2 and CLEC4M in normal human tissues

Fig 6 Interacting proteins of ACE2, CLEC4M and DPP4 involved in pathways and reactome pathways

Tab 3 Comparison of B cell epitopes of S protein in SARS-CoV-2 and SARS-CoV

Tab 4 Comparisonof Th epitopes of S protein in SARS-CoV-2 and SARS-CoV

Fig 7 Spatial locations of S protein epitopes in SARS-CoV-2 and SARS-CoV


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