生物技术通报 ›› 2021, Vol. 37 ›› Issue (10): 169-178.doi: 10.13560/j.cnki.biotech.bull.1985.2020-1474

• 研究报告 • 上一篇    下一篇

与SARS-CoV有交叉免疫反应的SARS-CoV-2 S蛋白B细胞抗原表位预测

高竞溪(), 高珂星, 鲁非, 纪锋, 郭志刚()   

  1. 南京师范大学生命科学学院,南京 210046
  • 收稿日期:2020-12-02 出版日期:2021-10-26 发布日期:2021-11-12
  • 作者简介:高竞溪,女,研究方向:抗体免疫;E-mail: 1669522990@qq.com
  • 基金资助:
    国家自然科学基金项目(81872284);江苏省自然科学基金(BE2018714)

Prediction of SARS-CoV-2 S Protein B Cell Antigenic Epitope Cross-immunizing with SARS-CoV

GAO Jing-xi(), GAO Ke-xing, LU Fei, JI Feng, GUO Zhi-gang()   

  1. School of Life Sciences,Nanjing Normal University,Nanjing 210046
  • Received:2020-12-02 Published:2021-10-26 Online:2021-11-12

摘要:

综合预测可与SARS-CoV发生交叉免疫反应的SARS-CoV-2 棘突蛋白(S蛋白)优势B细胞抗原表位,为开发SARS-CoV-2和SARS-CoV S蛋白通用表位疫苗和相关单抗奠定基础。采用MEGA5.05中的Neighbor-joining法构建基于SARS-CoV-2 S蛋白氨基酸序列的系统发生树;参考SARS-CoV-2毒株与SARS-CoV毒株S蛋白氨基酸序列比对及跨膜分析结果,筛选出二者可能存在的共同抗原表位区段(944-1 213aa)。以SARS-CoV-2 Wuhan-Hu-1株为研究对象,其目标区段的亲水性指数、柔性区段、蛋白质表面可能性和抗原指数等参数由DNAStar软件中的Protean模块进行分析预测;结合Phyre2在线工具模拟的空间结构,综合预测可与SARS-CoV发生交叉免疫反应的SARS-CoV-2 S蛋白B细胞优势抗原表位。SARS-CoV-2 S蛋白氨基酸序列与SARS-CoV S蛋白具有最高相似性(77.5%),与其它可感染人类的冠状病毒(MERS-CoV、HCoV-HKU1、HCoV-NL63、HCoV-229E)S蛋白存在显著差异,相似性均低于30.3%。Wuhan-Hu-1株S蛋白具有3个疏水核心,可能存在较强的可变性。目标B细胞抗原表位大概率分布于959-966、973-979、1 003-1 011、1 030-1 037、1 057-1 070、1 079-1 085、1 123-1 132、1 174-1 179位氨基酸区段。预测的SARS-CoV-2和SARS-CoV S蛋白共同抗原表位可为通用表位疫苗的设计、单抗的制备、相关药物的快速筛选等工作提供参考。

关键词: SARS-CoV-2, SARS-CoV, 棘突蛋白, B细胞抗原表位, 交叉免疫

Abstract:

Comprehensively predicting dominant B cell antigenicepitope of spike(S)protein in SARS-CoV-2 that can cross-immunize with SARS-CoV is to lay the foundation for the development of universal epitope vaccines and associated monoclonal antibodies of S protein in SARS-CoV-2 and SARS-CoV. We employed neighbor-joining method in MEGA5.05 to construct the phylogenetic tree based on the amino acid sequence of S protein in SARS-CoV-2. According to the amino acid sequence alignment of S proteins in SARS-CoV-2 and SARS-CoV and the corresponding results of transmembrane analysis,the region with common epitopes of the two proteins(944-1 213 aa)were screened out. Taking the target region of SARS-CoV-2 Wuhan-Hu-1 strain as the research object,we used the program Protean module in DNAStar software to analyze and predict parameters such as hydrophilicity,flexible region,surface possibility and antigenic index. Considering the spatial structure simulated by online tool Phyre2,we predicted the dominant B cell antigenic epitopes of the S protein in SARS-CoV-2 that cross-immunized with SARS-CoV. The amino acid sequence of the S protein in SARS-CoV-2 was the most similar to the S protein in SARS-CoV(77.5%),while it was significantly different from the S proteins in other coronaviruses(MERS-CoV,HCoV-HKU1,HCoV-NL63,and HCoV-229E),and their similarities were lower than 30.3%. The S protein in Wuhan-Hu-1 strain had three hydrophobic cores and might have strong mutability. The antigenic epitopes of target B cell were very likely in amino acid regions at 959-966,973-979,1 003-1 011,1 030-1 037,1 057-1 070,1 079-1 085,1 123-1 132 and 1 174-1 179. The predicted co-antigen epitopes of S proteins in SARS-CoV-2 and SARS-CoV may provide references for the design of universal epitope vaccines,production of monoclonal antibodies and rapid screening of related drugs.

Key words: SARS-CoV-2, SARS-CoV, spike protein, B cell antigenic epitope, cross immunity