新型冠状病毒棘突蛋白免疫原性分析及其多肽疫苗设计研究  

Epitope-based peptide vaccine design and immunogenicityanalysis of the spike protein from SARS-CoV-2

作　　者：许志强 鲁陈[2] 胡晓军[3] 郭有 胡巧丽 朱颖[2,4] XU Zhi-qiang;LU Chen;HU Xiao-jun;GUO You;HU Qiao-li;ZHU Ying(The First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210000;The First Affiliated Hospital of Gannan Medical University;Ganzhou Center for Disease Control and Prevention,Ganzhou,Jiangxi 341000;School of Life Science,Nanchang University,Nanchang,Jiangxi 330031)

机构地区：[1]南京医科大学第一附属医院,江苏南京210000 [2]赣南医学院第一附属医院 [3]赣州市疾病预防控制中心,江西赣州341000 [4]南昌大学生命科学学院,江西南昌330031

出　　处：《赣南医学院学报》2020年第3期217-224,共8页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：赣南医学院COVID-19应急项目(YJ202014)。

摘　　要：目的:分析新型冠状病毒(SARS-CoV-2)表面棘突蛋白的结构和B细胞表位。方法:首先利用Protparam对SARS-CoV-2棘突蛋白的物理化学性质特征进行分析。随后通过Clustal软件,对SARS-CoV-2和SARS-CoV棘突蛋白中的功能区域进行分析,并结合同源模拟,明确棘突蛋白的空间结构和折叠特征。综合DNAStar、ABCpred和BepiPred结果,筛选SARS-CoV-2棘突蛋白的线性B细胞表位,同时利用ElliPro、DiscoTope、SEPPA对棘突蛋白的构象B细胞表位进行综合预测。结果:通过同源模拟,SARS-CoV-2的棘突蛋白是同源三聚体结构,并且与SARS-CoV的棘突蛋白相似,也具有两种受体结合区域构象。通过综合多种免疫信息学工具及进一步筛选,11条线性表位(B9-B14和B27-B31)及5条构象表位(CB4-CB8)被筛出。结论:本研究筛选出的SARS-CoV-2棘突蛋白的16条B细胞表位,包括11条线性表位(B9-B14和B27-B31)及5条构象表位(CB4-CB8),可作为潜在的新型冠状病毒肺炎免疫原疫苗研发的候选表位。Objective:To analyse the structure and B-cell epitope of spike protein from SARS-CoV-2 surface.Methods:Firstly,the physiochemical properties of the SARS-Cov-2 spike protein were analyzed by the Protparam.Subsequently,the architecture of the SARS-CoV-2 spike protein was compared with that of SARS-CoV by sequence alignment in Clustal.The tertiary structure of SARS-CoV-2 spike protein was built by homologous modelling.Finally,both linear and conformational epitopes in spike protein were predicted by different immunoinformatic approaches including DNAStar,ABCpred,BepiPred,ElliPro,DiscoTope and SEPPA.Results:Through homologous simulation,the spike protein on SARS-CoV-2 was a homo-trimer and had two different conformations of receptor-binding domain which was similar with SARS-CoV.By combining multiple immunoinformatics tools and further screening,eleven linear epitopes(B9-B14 and B27-B31)and five conformational epitopes(CB4-CB8)were screened out.Conclusions:Sixteen B cell epitopes of SARS-CoV-2 spike protein,including eleven linear epitopes(B9-B14 and B27-B31)and five conformational epitopes(CB4-CB8),were suggested to be the potential candidate epitopes for the development of novel coronavirus pneumonia immunogenicity vaccine in the study.

关 键 词：新型冠状病毒 新型冠状病毒肺炎 三维结构模拟 B细胞表位 

分 类 号：R392.11[医药卫生—免疫学]