2019新型冠状病毒刺突蛋白表位预测及变异分析

Potential epitopes and mutation characteristics of 2019 novel coronavirus spike protein

目的预测2019新型冠状病毒(2019 novel coronavirus,2019-nCoV)刺突蛋白的抗原表位,分析刺突蛋白的变异规律。方法从基因库(GenBank)和全球共享禽流感数据倡议组织数据库下载2019-nCoV的基因序列(截至2020年3月4日)。应用ClustalW、MEGA 7.0、免疫表位数据库等生物信息学软件,预测刺突蛋白潜在的B淋巴细胞和T淋巴细胞表位,分析比较刺突蛋白的变异在表位区与非表位区的特点。统计学分析采用χ^2检验。结果刺突蛋白有130个潜在表位,包括25个线性B淋巴细胞表位、18个非线性B淋巴细胞表位、71个人类白细胞抗原(human leukocyte antigen,HLA)Ⅰ类限制性T淋巴细胞表位和16个HLAⅡ类限制性T淋巴细胞表位。S404-426肽段有较高的抗原性,且在中国的人群覆盖率达73.4%。与1月31日之前的2019-nCoV刺突蛋白相比,其在1月31日之后的变异频率在非表位区(15.4%比21.7%)和表位区(6.2%比8.7%)都有所增加,但差异均无统计学意义(均P>0.05)。结论2019-nCoV刺突蛋白有多个抗原表位,为2019-nCoV疫苗的研究提供了参考依据。刺突蛋白的变异有增加趋势,需进一步关注和研究。

Objective To predict the epitopes of the spike protein of 2019 novel coronavirus(2019-nCoV)and to analyze the mutation characteristics of this protein.Methods The gene sequences of 2019-nCoV was downloaded from GenBank and Global Initiative on Sharing All Influenza Data database(as of March 4,2020).ClustalW,MEGA 7.0,Immune Epitope Database and other software were used for predicting potential B lymphocyte and T lymphocyte epitopes of spike protein,and then mutations were compared in epitope and non-epitope regions.Statistical analysis was performed with chi-square test.Results There were 130 potential epitopes,including 25 linear B lymphocyte epitopes,18 non-linear B lymphocyte epitopes,71 human leukocyte antigen(HLA)class-Ⅰrestricted T lymphocyte epitopes,and 16 HLA class-Ⅱrestricted T lymphocyte epitopes in spike protein.S404-426displayed the higher antigenicity-score,and its population coverage was 73.4%in China.Compared with the spike protein before January 31,the mutation frequencies of spike protein were increased both in non-epitope(15.4%vs 21.7%)and epitope regions(6.2%vs 8.7%)after January 31,but the differences were not statistically significant(both P>0.05).Conclusions The study identifies several epitopes of 2019-nCoV spike protein,which provides a preliminary basis for the study of 2019-nCoV vaccine.Mutations in spike protein have an increasing trend which needs more attention and research in the future.