摘要
2019年12月,由SARS-CoV-2感染引起新型冠状病毒肺炎在武汉暴发。世界卫生组织(WHO)于2020年3月11日宣布新冠肺炎疫情已构成全球性大流行,给世界各国造成了巨大的人员伤亡和经济损失。SARS-CoV-2的S蛋白是核衣壳表面的刺突蛋白,介导病毒与细胞受体结合及膜融合,是疫苗、治疗性抗体的研发以及临床诊断的关键靶点。为了分析SARS-CoV-2表面S蛋白的突变情况,我们以武汉分离株Wuhan-Hu-1(GenBank登录号:MN908947.3)为标准株,利用生物信息学方法,对SARS-CoV-2 S蛋白的突变位点及其对蛋白质结构和功能的影响进行分析。截至2020年4月17日,GenBank数据库中有1002株SARS-CoV-2毒株,其中仅有12株病毒S蛋白氨基酸序列发生了突变。其中一些突变可影响S蛋白的理化性质和二级结构。R408I位氨基酸位于受体结合结构域(RBD)内且位于蛋白表面,突变可能会影响RBD结构。48、74、181、221、655位突变氨基酸位于预测的B细胞线性表位内,其中74、181、655位氨基酸突变对B细胞线性表位结构和性质产生较大影响。分离自人、犬、猫等宿主的SARS-CoV-2的S蛋白高度保守,而分离自老虎的毒株存在D614G突变。与蝙蝠冠状病毒相比,SARS-CoV-2的S蛋白存在独特的弗林蛋白酶识别位点。结果表明,SARS-CoV-2表面S蛋白在种内和种间都较为保守,但仍然存在一些突变位点,可以影响S蛋白的理化性质和结构,进而影响病毒与受体的亲和力以及病毒的传染性。以上数据将为药物、抗体、疫苗等研发工作提供线索。
In December 2019,a new type of pneumonia,coronavirus disease 2019(COVID-19),caused by a novel coronavirus,SARS-CoV-2,was detected in hospitals in Wuhan,Hubei Province,China.The World Health Organization announced on 11 March 2020 that COVID-19 can be characterized as a pandemic,and since then COVID-19 has wrought havoc on public-health systems worldwide.The surface"spike"protein(S protein)of SARS-CoV-2 mediates host-cell attachment and membrane fusion.The S protein is a key target for urgent development of vaccines,therapeutic antibodies,and diagnostics.To analyze the mutations and their effects on protein structure and function of the S protein,bioinformatics software has been used to analyze its nucleotide and amino-acid sequences,and Wuhan-Hu-1(GenBank accession number:MN908947.3)was used as standard strain.As of 17 April 2020,there were 1,002 SARS-CoV-2 strains in the GenBank database,of which 12 strains had mutations in the amino-acid sequence of the S protein.Some of these mutations could affect the physicochemical properties and secondary structures of the S protein.The R408 I mutation was located in the receptor-binding domain(RBD)and displayed on the surface,and could affect the RBD structure.The mutated amino acids 48,74,181,221 and 655 were located in predicted linear epitopes of B cells,and 74,181 and 655 mutations could greatly affect the structures and properties of linear epitopes of B cells.The S protein of SARSCoV-2 isolated from humans,dogs,cats and lions was highly conserved,whereas the D614 G mutation was found in the isolated strain from tigers.Furthermore,the unique flynn protease recognition site was presented in the S protein of SARS-CoV-2 compared with the coronavirus from bats.These results suggest that the S protein of SARS-CoV-2 is relatively conserved within and between species,whereas there are some mutations that can affect the physicochemical properties and structures of the S protein,which may also affect the linear epitopes of B cells.Taken together,these data provide a basis for the research and development of drugs,antibodies and vaccines against SARS-CoV-2.
作者
毛亚萍
卞大伟
MAO Yaping;BIAN Dawei(School of Public Health,Shenyang Medical College,Shenyang 110034,China;Liaoning Agricultural Development Service Center,Shenyang 110003,China)
出处
《病毒学报》
CAS
CSCD
北大核心
2020年第6期1020-1027,共8页
Chinese Journal of Virology
作者简介
毛亚萍(1987-),女,汉族,博士研究生,讲师,从事动物分子病毒学研究,E-mail:maoyaping195@163.com;通讯作者:毛亚萍(1987-),女,汉族,博士研究生,讲师,从事动物分子病毒学研究,E-mail:maoyaping195@163.com。
