摘要
新型冠状病毒病(coronavirus disease 2019,COVID-19)的病原体为新型冠状病毒(COVID-19 virus),以下简称为新冠病毒,也称为severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).研究认为,SARS-CoV-2可能起源于蝙蝠,但是其中间宿主仍不清楚.目前,除蝙蝠外,穿山甲被证明是唯一携带SARS-CoV-2相关冠状病毒的哺乳动物,因而被认为是可能的中间宿主.本研究利用表面等离子共振实验(surface plasmon resonance,SPR)展现和分析了SARS-CoV-2和两种穿山甲冠状病毒(pangolin-CoVs,GX/P2V/2017和GD/1/2019)分别与穿山甲ACE2(pangolin ACE2,pACE2)和人ACE2(human ACE2,hACE2)受体的结合能力,解析了SARS-CoV-2刺突蛋白(spike,S)受体结合域(receptor binding domain,RBD)与pACE2复合物的晶体结构,分辨率为2.3Å,发现SARS-CoV-2 RBD结合pACE2的模式与结合hACE2或猫ACE2(cat ACE2,cACE2)相似,但与hACE2更相近.通过同源建模的方式,进一步模拟了GX/P2V/2017 RBD和GD/1/2019 RBD分别与pACE2和hACE2受体的结合,发现二者结合pACE2和hACE2的方式与SARS-CoV-2 RBD相似,但晶体结构或同源建模的数据暗示,上述3种RBDs结合pACE2的能力均稍弱于hACE2,这与SPR的结论一致.这些研究结果不仅有助于我们更好地理解SARS-CoV-2的进化,而且警示我们穿山甲冠状病毒具有感染人的潜力,强调了持续监测穿山甲携带病毒的重要性,以防止病毒外溢,引起人类疾病.
The virus caused coronavirus disease 2019(COVID-19 virus),also called severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is the seventh coronavirus that can infect humans,and belongs to the genusβ-coronavirus in the family Coronaviridae.As of 5 November 2020,SARS-CoV-2 has caused>47000000 confirmed cases and>1200000 related deaths in 219 countries and regions,bringing great challenges to global public health.Currently,there is no approved therapeutics or vaccines for the treatment of this disease.Several studies suggested SARS-CoV-2 might have originated from bats based on phylogenetic analysis,but the intermediate host of the virus is still unknown.Besides humans,cats,dogs,tigers,lions,minks,and other species have been reported to be infected by SARS-CoV-2.Several studies have reported pangolins as the only other mammalian species carrying coronaviruses related to SARS-CoV-2 besides bats,and suggested pangolins might be the intermediate host of SARS-CoV-2.Previously,we and other groups identified the angiotensin converting enzyme 2(ACE2),the receptor of SARS-CoV,also functions as the entry receptor of SARS-CoV-2 and is recognized by the receptor binding domain(RBD)of the spike protein(S).Then,we elucidated the interaction between SARS-CoV-2 RBD and human ACE2(hACE2)or cat ACE2(cACE2),and also found that SARS-CoV-2 had broad potential host range,including domestic animals,companion pets and wild animals.In this study,we investigated the binding features of SARS-CoV-2 and two pangolin coronaviruses(pangolin-CoVs,GX/P2V/2017 and GD/1/2019)that recognize the receptors of both pangolin ACE2(pACE2)and hACE2 using surface plasmon resonance(SPR)and structural methods.We further determined the crystal structure of SARS-CoV-2 S(RBD)in complex with pACE2 at a 2.3Åresolution,revealing the similarity in the binding mode between SARS-CoV-2 RBD to hACE2 and to cACE2.Interestingly,we found that the SARS-CoV-2 RBD-pACE2 complex is more similar to the SARS-CoV-2 RBD-hACE2 complex than to SARS-CoV-2 RBD-cACE2 complex.Fu
作者
仵丽丽
苏佳岐
牛胜
陈茜
张艳芳
严景华
施一
齐建勋
高福
王奇慧
Lili Wu;Jiaqi Su;Sheng Niu;Qian Chen;Yanfang Zhang;Jinghua Yan;Yi Shi;Jianxun Qi;George Fu Gao;Qihui Wang(CAS Key Laboratory of Microbial Physiological and Metabolic Engineering,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China;College of Animal Science and Veterinary Medicine,Shanxi Agricultural University,Taigu 030801,China;Institute of Physical Science and Information,Anhui University,Hefei 230039,China;Savaid Medical School,University of Chinese Academy of Sciences,Beijing 100049,China)
出处
《科学通报》
EI
CAS
CSCD
北大核心
2021年第1期73-84,共12页
Chinese Science Bulletin
基金
中国科学院战略性先导科技专项(XDB29010202)
国家自然科学基金(81922044)
中国科学院“青年创新促进会”项目(2018119)资助。
