鲁荣光;武婧;白雪;刘维全;

• 1:中国农业科学院特产研究所农业农村部经济动物疫病重点实验室
• 2:中国农业大学生物学院农业生物技术国家重点实验室

摘要(Abstract)：

由新型冠状病毒(SARS-CoV-2)引起的冠状病毒病2019(COVID-19)作为一种新发传染病,已经蔓延到全世界的多个国家和地区,被WHO判定为全球大流行病(Pandemic disease),引发了严重的公共卫生安全问题。自SARS-CoV-2出现以来,病毒溯源和中间宿主等问题得到了民众的广泛关注,虽然只有约2%的感染者有野生动物接触史,但科学家普遍认为SARS-CoV-2是一种来自野生动物的病毒。病毒的跨种属传播十分困难,而且往往会引起新宿主的高病死率,但SARS-CoV-2被发现以来,表现出对人类机体已经有了很好的适应性,具有传播能力强和病死率较低的特性,这与之前发现的引起新发、突发传染病的大多数病毒有所不同。因此,本文对SARS-CoV-2的病原学,功能受体和基因组进化等方面的研究进展进行综述,以期为SARS-CoV-2的溯源提供新的视角。

关键词(KeyWords)： 新型冠状病毒;研究进展;ACE2

Abstract:

Keywords:

基金项目(Foundation): “十三五”重点研发计划(2016YFD0501000)子课题(2016YFD0501001);; 中国农业科学院科技创新工程(CAAS-ASTIP-2016-ISAPS)~~

作者(Authors): 鲁荣光;武婧;白雪;刘维全;

DOI: 10.13242/j.cnki.bingduxuebao.003699

参考文献(References)：

• [1]Wu F,Zhao S,Yu B,Chen Y M,Wang W,Song ZG,Hu Y,Tao Z W,Tian J H,Pei Y Y,Yuan M L,Zhang Y L,Dai F H,Liu Y,Wang Q M,Zheng J J,Xu L,Holmes E C,Zhang Y Z.A new coronavirus associated with human respiratory disease in China[J].Nature,2020,579,265-269.
• [2]Zhu N,Zhang D,Wang W,Li X,Yang B,Song J,Zhao X,Huang B,Shi W,Lu R,Niu P,Zhan F,Ma X,Wang D,Xu W,Wu G,Gao G F,Tan W,China Novel Coronavirus Investigating and Research Team.ANovel Coronavirus from Patients with Pneumonia in China,2019[J].N Engl J Med,2020,382(8):727-733.
• [3]Zhou P,Yang X L,Wang X G,Hu B,Zhang L,Zhang W,Si H R,Zhu Y,Li B,Huang C L,Chen HD,Chen J,Luo Y,Guo H,Jiang R D,Liu M Q,Chen Y,Shen X R,Wang X,Zheng X S,Zhao K,Chen QJ,Deng F,Liu L L,Yan B,Zhan F X,Wang Y Y,Xiao G F,Shi Z L.A pneumonia outbreak associated with a new coronavirus of probable bat origin[J/OL].Nature,2020,579(7798):270-273.
• [4]Jiang S,Shi Z,Shu Y,Song J,Gao G F,Tan W,Guo D.A distinct name is needed for the new coronavirus[J].Lancet,2020,395(10228):949.
• [5]Coronaviridae Study Group of the International Committee on Taxonomy of Viruses.The species Severe acute respiratory syndrome-related coronavirus:classifying 2019-n Co V and naming it SARS-Co V-2[J/OL].Nat Microbiol,2020,5(4):536-544
• [6]Yeager C L,Ashmun R A,Williams R K,Cardellichio C B,Shapiro L H,Look A T,Holmes K V.Human aminopeptidase N is a receptor for human coronavirus229E[J].Nature,1992,357(6377):420-422.
• [7]Mathewson A C,Bishop A,Yao Y,Kemp F,Ren J,Chen H,Xu X,Berkhout B,Van Der Hoek L,Jones IM.Interaction of severe acute respiratory syndromecoronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2[J].J Gen Virol,2008,89(Pt 11):2741-2745.
• [8]Zhu Y,Li C,Chen L,Xu B,Zhou Y,Cao L,Shang Y,Fu Z,Chen A,Deng L,Bao Y,Sun Y,Ning L,Liu C,Yin J,Xie Z,Shen K.A novel human coronavirus OC43 genotype detected in China's mainland[J].Emerg Microbes Infect,2019,7(1):1-4.
• [9]Lau S K P,Woo P C Y,Yip C C Y,Tse H,Tsoi HW,Cheng V C C,Lee P,Tang B S F,Cheung C HY,Lee R A,So L Y,Lau Y L,Chan K H,Yuen K Y.Coronavirus HKU1 and Other Coronavirus Infections in Hong Kong[J].J Clin Microbiol,2006,44(6):2063-2071.
• [10]Cui J,Li F,Shi Z L.Origin and evolution of pathogenic coronaviruses[J].Nat Rev Microbiol,2019,17(3):181-192.
• [11]Lefkowitz E J,Dempsey D M,Hendrickson R C,Orton R J,Siddell S G,Smith D B.Virus taxonomy:the database of the International Committee on Taxonomy of Viruses(ICTV)[J].Nucleic Acids Res,2018,46(D1):D708-D717.
• [12]Li F.Receptor recognition and cross-species infections of SARS coronavirus[J].Antiviral Res,2013,100(1):246-254.
• [13]Licitra B N,Duhamel G E,Whittaker G R.Canine enteric coronaviruses:emerging viral pathogens with distinct recombinant spike proteins[J].Viruses,2014,6(8):3363-3376.
• [14]Felten S,Hartmann K.Diagnosis of feline infectious peritonitis:A Review of the current literature[J].Viruses,2019,11(11):1068.
• [15]王楷宬,庄青叶,邱源,侯广宇.水貂冠状病毒中国分离株全基因序列测定及分析[J].中国动物检疫,2017,34(12):88-91.
• [16]Schultze B,Herrler G.Bovine coronavirus uses N-acetyl-9-O-acetylneuraminic acid as a receptor determinant to initiate the infection of cultured cells[J].J Gen Virology,73(4):901-906.
• [17]Vijgen L,Keyaerts E,Lemey P,Maes P,Van Reeth K,Nauwynck H,Pensaert M,Van Ranst M.Evolutionary history of the closely related group 2coronaviruses:porcine hemagglutinating encephalomyelitis virus,bovine coronavirus,and human coronavirus OC43[J].J Virol,2006,80(14):7270-7274.
• [18]Cook J K A,Jackwood M,Jones R C.The long view:40 years of infectious bronchitis research[J].Avian Pathology,41(3):239-250.
• [19]Fu J,Chen R,Hu J,Qu H,Zhao Y,Cao S,Wen X,Wen Y,Wu R,Zhao Q,Ma X,Huang X.Identification of a novel linear B-cell epitope on the nucleocapsid protein of porcine deltacoronavirus[J].Int J Mol Sci,2020,21(2):648.
• [20]Weiss S R,Leibowitz J L.Coronavirus pathogenesis[J].Adv Virus Res,2011,81(85-164).
• [21]Winter C,Schwegmann-Wessels C,Cavanagh D,Neumann U,Herrler G.Sialic acid is a receptor determinant for infection of cells by avian infectious bronchitis virus[J].J Gen Virol,2006,87(Pt 5):1209-1216.
• [22]Tresnan D B,Levis R,Holmes K V.Feline aminopeptidase N serves as a receptor for feline,canine,porcine,and human coronaviruses in serogroup I[J].JVirol,1996,70(12):8669-8674.
• [23]Delmas B,Gelfi J,L'haridon R,Vogel,Sj?str?m H,Norén,Laude H.Aminopeptidase N is a major receptor for the enteropathogenic coronavirus TGEV[J].Nature,1992,357(6377):417-420.
• [24]Hamming I,Timens W,Bulthuis M L,Lely A T,Navis G,Van Goor H.Tissue distribution of ACE2protein,the functional receptor for SARS coronavirus.A first step in understanding SARS pathogenesis[J].JPathol,2004,203(2):631-637.
• [25]Barlan A,Zhao J,Sarkar M K,Li K,Mccray P B,Jr.,Perlman S,Gallagher T.Receptor variation and susceptibility to Middle East respiratory syndrome coronavirus infection[J].J Virol,2014,88(9):4953-4961.
• [26]Reguera J,Mudgal G,Santiago C,Casasnovas J M.Astructural view of coronavirus-receptor interactions[J].Virus Res,2014,194,3-15.
• [27]Williams R K,Jiang G S,Holmes K V.Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins[J].Proc Natl Acad Sci,88(13):5533-5536.
• [28]Dveksler G S,Pensiero M N,Cardellichio C B,Williams R K,Jiang G S,Holmes K V,Dieffenbach CW.Cloning of the mouse hepatitis virus (MHV)receptor:expression in human and hamster cell lines confers susceptibility to MHV[J].J Virol,1991,65(12):6881-6891.
• [29]Wang B,Liu Y,Ji C M,Yang Y L,Liang Q Z,Zhao P,Xu L D,Lei X M,Luo W T,Qin P,Zhou J,Huang Y W.Porcine deltacoronavirus engages the transmissible gastroenteritis virus functional receptor porcine aminopeptidase N for infectious cellular entry[J/OL].J Virol,2018,92(12):e00318-18.
• [30]Wan Y,Shang J,Graham R,Baric R S,Li F.Receptor recognition by novel coronavirus from Wuhan:An analysis based on decade-long structural studies of SARS[J].J Virol,2020.DOI:10.1128/JVI.00127-20.
• [31]Lu R,Zhao X,Li J,Niu P,Yang B,Wu H,Wang W,Song H,Huang B,Zhu N,Bi Y,Ma X,Zhan F,Wang L,Hu T,Zhou H,Hu Z,Zhou W,Zhao L,Chen J,Meng Y,Wang J,Lin Y,Yuan J,Xie Z,Ma J,Liu W J,Wang D,Xu W,Holmes E C,Gao G F,Wu G,Chen W,Shi W,Tan W.Genomic characterisation and epidemiology of 2019 novel coronavirus:implications for virus origins and receptor binding[J].Lancet,2020,395(10224):565-574.
• [32]Li W,Moore M J,Vasilieva N,Sui J,Wong S K,Berne M A,Somasundaran M,Sullivan J L,Luzuriaga K,Greenough T C.Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus[J].Nature,2003,426(6965):450-454.
• [33]Bao L,Deng W,Huang B,Gao H,Ren L,Wei Q,Yu P,Xu Y,Liu J,Qi F,Qu Y,Wang W,Li F,Lv Q,Xue J,Gong S,Liu M,Wang G,Wang S,Zhao L,Liu P,Zhao L,Ye F,Wang H,Zhou W,Zhu N,Zhen W,Yu H,Zhang X,Song Z,Guo L,Chen L,Wang C,Wang Y,Wang X,Xiao Y,Sun Q,Liu H,Zhu F,Ma C,Yan L,Yang M,Han J,Xu W,Tan W,Peng X,Jin Q,Wu G,Qin C.The Pathogenicity of SARS-Co V-2 in h ACE2 Transgenic Mice[J].bio Rxiv,2020.DOI:https：//doi.org/10.1101/2020.02.07.939389
• [34]Yan R,Zhang Y,Li Y,Xia L,Guo Y,Zhou Q.Structural basis for the recognition of the SARS-Co V-2by full-length human ACE2[J/OL].Science,2020.DOI:10.1126/science.abb2762
• [35]Wrapp D,Wang N,Corbett K S,Goldsmith J A,Hsieh C-L,Abiona O,Graham B S,Mclellan J S.2020.DOI:10.2210/pdb6VSB/pdb
• [36]Imai Y,Kuba K,Ohto-Nakanishi T,Penninger J M.Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis[J].Circ J,2010,74(3):405-410.
• [37]Zhe Xu,L S,Yijin Wang,Jiyuan Zhang,Lei Huang,Chao Zhang,Shuhong Liu,Peng Zhao,Hongxia Liu,Li Zhu,Yanhong Tai,Changqing Bai,,Tingting Gao JS,Peng Xia,Jinghui Dong,Jingmin Zhao,Fu-Sheng Wang.Pathological findings of COVID-19 associated with acuterespiratory distress syndrome[J/OL].Lancet Respir Med,2020.DOI:https：//doi.org/10.1016/S2213-2600(20)30076-X
• [38]Yeo C,Kaushal S,Yeo D.Enteric involvement of coronaviruses:is faecal-oral transmission of SARS-Co V-2 possible?[J].Lancet Gastroenterol Hepatol,2020,5(4):335-337.
• [39]Young B E,Ong S W X,Kalimuddin S,Low J G,Tan S Y,Loh J,Ng O T,Marimuthu K,Ang L W,Mak TM,Lau S K,Anderson D E,Chan K S,Tan T Y,Ng T Y,Cui L,Said Z,Kurupatham L,Chen M I,Chan M,Vasoo S,Wang L F,Tan B H,Lin R T P,Lee VJ M,Leo Y S,Lye D C,Singapore Novel Coronavirus Outbreak Research T.Epidemiologic features and clinical course of patients infected with SARS-Co V-2 in singapore[J/OL].JAMA,2020.DOI:10.1001/jama.2020.3204
• [40]Larkin M A,Blackshields G,Brown N P,Chenna R,Mcgettigan P A,Mcwilliam H,Valentin F,Wallace IM,Wilm A,Lopez R,Thompson J D,Gibson T J,Higgins D G.Clustal W and Clustal X version 2.0[J].Bioinformatics,2007,23(21):2947-2948
• [41]Kumar S,Stecher G,Li M,Knyaz C,Tamura K,Battistuzzi F U.MEGA X:Molecular Evolutionary Genetics Analysis across Computing Platforms[J].Mol Biol Evol,2018,35(6):1547-1549.
• [42]吴祖建,高芳銮,沈建国.生物信息学分析实践[M].北京：科学出版社,2010:149-180.
• [43]Li F,Li W,Farzan M,Harrison S.Structure of SARScoronavirus spike receptor-binding domain complexed with receptor[J].Science,309(5742):1864-1868.
• [44]Li R,Qiao S,Zhang G.Analysis of angiotensinconverting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-n Co V[J/OL].J Infect,2020.DOI:https：//doi.org/10.1016/j.jinf.2020.02.013.
• [45]Li W,Wong S K,Li F,Kuhn J H,Huang I C,Choe H,Farzan M.Animal origins of the severe acute respiratory syndrome coronavirus:insight from ACE2-S-protein interactions[J].J Virol,2006,80(9):4211-4219.
• [46]Zhong N S,Zheng B J,Li Y M,Poon,Xie Z H,Chan K H,Li P H,Tan S Y,Chang Q,Xie J P,Liu X Q,Xu J,Li D X,Yuen K Y,Peiris,Guan Y.Epidemiology and cause of severe acute respiratory syndrome(SARS)in Guangdong,People's Republic of China,in February,2003[J].Lancet (London,England),2003,362(9393):1353-1358.
• [47]Zheng B J,Wong K H,Zhou J,Wong K L,Young BW Y,Lu L W,Lee S S.SARS-related virus predating SARS outbreak,Hong Kong[J].Emerging Infect Dis,2004,10(2):176-178.
• [48]Kan B,Wang M,Jing H,Xu H,Jiang X,Yan M,Liang W,Zheng H,Wan K,Liu Q,Cui B,Xu Y,Zhang E,Wang H,Ye J,Li G,Li M,Cui Z,Qi X,Chen K,Du L,Gao K,Zhao Y-T,Zou X-Z,Feng Y-J,Gao Y-F,Hai R,Yu D,Guan Y,Xu J.Molecular evolution analysis and geographic investigation of severe acute respiratory syndrome coronavirus-like virus in palm civets at an animal market and on farms[J].J Virol,2005,79(18):11892-11900.
• [49]Tu C,Crameri G,Kong X,Chen J,Sun Y,Yu M,Xiang H,Xia X,Liu S,Ren T,Yu Y,Eaton B T,Xuan H,Wang L-F.Antibodies to SARS coronavirus in civets[J].Emerging Infect Dis,2004,10(12):2244-2248.
• [50]Martina B E E,Haagmans B L,Kuiken T,Fouchier Ra M,Rimmelzwaan G F,Van Amerongen G,Peiris J SM,Lim W,Osterhaus A D M E.Virology:SARSvirus infection of cats and ferrets[J].Nature,2003,425(6961):915-915.
• [51]Lun Z R,Qu L H.Animal-to-human SARS-associated coronavirus transmission?[J].Emerging Infect Dis,2004,10(5):959-959.
• [52]Guan W J,Ni Z Y,Hu Y,Liang W H,Ou C Q,He JX,Liu L,Shan H,Lei C L,Hui D S C,Du B,Li L J,Zeng G,Yuen K Y,Chen R C,Tang C L,Wang T,Chen P Y,Xiang J,Li S Y,Wang J L,Liang Z J,Peng Y X,Wei L,Liu Y,Hu Y H,Peng P,Wang JM,Liu J Y,Chen Z,Li G,Zheng Z J,Qiu S Q,Luo J,Ye C J,Zhu S Y,Zhong N S,China Medical Treatment Expert Group For C.Clinical Characteristics of Coronavirus Disease 2019 in China[J/OL].N Engl JMed,2020.DOI:10.1056/NEJMoa2002032.
• [53]Hu B,Zeng L P,Yang X L,Ge X Y,Zhang W,Li B,Xie J Z,Shen X R,Zhang Y Z,Wang N,Luo D S,Zheng X S,Wang M N,Daszak P,Wang L F,Cui J,Shi Z L.Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus[J/OL].PLo S Pathog,2017,13(11):e1006698.
• [54]Liu P,Chen W,Chen J P.Viral metagenomics revealed sendai virus and coronavirus infection of Malayan Pangolins (Manis javanica)[J].Viruses,2019,11(11):979.
• [55]Xiao K,Zhai J,Feng Y,Zhou N,Zhang X,Zou J J,Li N,Guo Y,Li X,Shen X,Zhang Z,Shu F,Huang W,Li Y,Zhang Z,Chen R A,Wu Y J,Peng S M,Huang M,Xie W J,Cai Q H,Hou F H,Liu Y,Chen W,Xiao L,Shen Y.Isolation and characterization of2019-n Co V-like coronavirus from Malayan Pangolins[J].bio Rxiv 2020.DOI:https：//doi.org/10.1101/2020.02.17.951335.
• [56]Rivers T M.Viruses and Koch's postulates[J].JBacteriol,1937,33(1):1-12.
• [57]董雅琴,张慧,张锋,刘爽,崔进,李晓成,魏荣.猪源冠状病毒监测简报[J].中国动物检疫,2020,37(3):1-2.
• [58]王楷宬,李阳,庄青叶,姜利建,张富友,姜楠,刘华雷.禽源冠状病毒监测简报[J].中国动物检疫,2020,37(2):1-2.
• [59]崔尚金,赵花芬,纪志辉,石文达,熊国英,梁琳,陈海博,王祉国,刘坡,韩武,张伟,王宏伟.对24例宠物临诊病例检测未发现新型冠状病毒(SARS-Co V-2)核酸阳性[J].病毒学报,2020,36(2):170-175.DOI:https：//doi.org/10.13242/j.cnki.bingduxuebao.003650
• [60]Song Z,Xu Y,Bao L,Zhang L,Yu P,Qu Y,Zhu H,Zhao W,Han Y,Qin C.From SARS to MERS,Thrusting Coronaviruses into the Spotlight[J].Viruses,2019,11(1):59
• [61]Hellewell J,Abbott S,Gimma A,Bosse N I,Jarvis CI,Russell T W,Munday J D,Kucharski A J,Edmunds W J,Centre for the Mathematical Modelling of Infectious Diseases C-W G,Funk S,Eggo R M.Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts[J].Lancet Global Health,2020,S2214-2109X(2220)30074-30077.
• [62]Chen S,Yang J,Yang W,Wang C,B?rnighausen T.COVID-19 control in China during mass population movements at New Year[J].Lancet (London,England),2020,S0140-6736(0120)30421-30429.
• [63]Karupiah G.Fields Virology,4TH EDITION[J].Immunol Cell Biol,2002,80(3):314-315.
• [64]张原.SARS冠状病毒的分子进化研究[D].复旦大学,2007.