nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo searchdiv qikanlogo popupnotification paper paperNew
2020, 06, v.36 1165-1170
新型冠状病毒受体血管紧张素转换酶2的研究进展
基金项目(Foundation):
邮箱(Email): yifanfengshun2298@163.com;
DOI: 10.13242/j.cnki.bingduxuebao.003824
摘要:

自新型冠状病毒肺炎暴发以来,中国已累计超过8万例患者。随着对其病毒结构和感染机制的深入研究,研究者们发现血管紧张素转换酶(Angiotensin converting enzyme,ACE)2是新型冠状病毒(SARS-CoV-2)的受体。根据既往的研究,ACE2是肾素血管紧张素系统(Renin angiotensin system,RAS)的关键酶之一,与其同源物ACE在该系统中起协同调节作用,同时,其生理调节功能也广泛作用于心血管、肾脏、肝脏、肠道等。疫情暴发后,人们急于了解SARS-CoV-2的溯源、中间宿主、流行病学分析和治疗的靶点,ACE2身份的转变使其成为研究的热点之一。本文就目前ACE2在SARS-CoV-2和心血管等领域的研究进展进行简要综述,以期为SARS-CoV-2的溯源、跨物种传播、流行病学分析以及抗病毒药物靶点研究提供参考依据。

Abstract:

There have been nearly 80,000 cases in the world since the outbreak of novel coronavirus pneumonia.With the study on viral structure and infection mechanism,researchers have found that angiotensin converting enzyme 2(ACE2)is the receptor of SARS-CoV-2. According to previous studies,ACE2 is one of the key enzymes in the RAS system. It plays a regulatory role with its homologue,namely ACE. The physiological function can be found in angiocarpy,kidney,liver,intestine and so on. The outbreak of novel coronavirus pneumonia makes people eager to know the viral source,intermediate host,epidemiological analysis and therapeutic targets. Then ACE2 becomes a research hotspot. In this review,we discuss the research advance of ACE2 in SARS-CoV-2 and cardiovascular diseases to provide references for tracing, cross-species transmission,epidemiological analysis and antiviral treatment of SARS-CoV-2.

参考文献

[1] Kuba K,Imai Y,Rao S,Gao H,Guo F,Guan B,Huan Y,Yang P,Zhang Y,Deng W. A crucial role of angiotensin converting enzyme 2(ACE2)in SARS coronavirus–induced lung injury[J]. Nat Med,2005,11(8):875-879.

[2] 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.

[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. A pneumonia outbreak associated with a new coronavirus of probable bat origin[J]. Nature,2020,579(7798):270-273.

[4]关贵文,高林,王建文,文夏杰,毛天皓,彭思雯,张婷,陈香梅,鲁凤民.新型冠状病毒感染肺炎患者肝酶异常的机制探究[J].中华肝脏病杂志,2020,28(2):100-106.

[5] Santos R A S,Sampaio W O,Alzamora A C,MottaSantos D,Alenina N,Bader M,Campagnole-Santos M J. The ACE2/angiotensin-(1–7)/MAS axis of the renin-angiotensin system:focus on angiotensin-(1–7)[J].Physiol Rev,2018,98(1):505-553.

[6] Kuba K,Imai Y,Rao S,Jiang C,Penninger J M.Lessons from SARS:control of acute lung failure by the SARS receptor ACE2[J]. J Mol Med,2006,84(10):814-820.

[7] Crackower M A, Sarao R, Oudit G Y, Yagil C,Kozieradzki I,Scanga S E,Oliveira-dos-Santos A J,da Costa J, Zhang L, Pei Y. Angiotensin-converting enzyme 2 is an essential regulator of heart function[J].Nature,2002,417(6891):822-828.

[8] Ortiz-Pérez J T,Riera M,Bosch X,De Caralt T M,Perea R J,Pascual J,Soler M J. Role of circulating angiotensin converting enzyme 2 in left ventricular remodeling following myocardial infarction:a prospective controlled study[J/OL]. PLoS One,2013,8(4):e61695.

[9] Ferrario C M. Cardiac remodelling and RAS inhibition[J]. Ther Adv Cardiovasc Dis,2016,10(3):162-171.

[10]Te Riet L,van Esch J H,Roks A J,van den Meiracker A H,Danser A J. Hypertension:renin–angiotensin–aldosterone system alterations[J]. Circ Res,2015,116(6):960-975.

[11]Lu N,Yang Y,Wang Y,Liu Y,Fu G,Chen D,Dai H,Fan X,Hui R,Zheng Y. ACE2 gene polymorphism and essential hypertension:an updated meta-analysis involving 11,051 subjects[J]. Mol Biol Rep,2012,39(6):6581-6589.

[12]Yang M, Zhao J, Xing L, Shi L. The association between angiotensin-converting enzyme 2polymorphisms and essential hypertension risk:A metaanalysis involving 14, 122 patients[J]. J Renin Angiotensin Aldosterone Syst,2015,16(4):1240-1244.

[13]La De Maria M,D Araújo L,A Fraga-Silva R,AS Pereira L,J Ribeiro H,B Menezes G,Shenoy V,K Raizada M,J Ferreira A. Anti-hypertensive effects of diminazene aceturate:an angiotensin-converting enzyme2 activator in rats[J]. Protein Pept Lett,2016,23(1):9-16.

[14]Marra M A,Jones S J,Astell C R,Holt R A,BrooksWilson A,Butterfield Y S,Khattra J,Asano J K,Barber S A,Chan S Y. The genome sequence of the SARS-associated coronavirus[J]. Science,2003,300(5624):1399-1404.

[15]Li F. Structure,function,and evolution of coronavirus spike proteins[J]. Annu Rev Virol,2016,3:237-261.

[16]Imai Y,Kuba K,Rao S,Huan Y,Guo F,Guan B,Yang P,Sarao R,Wada T,Leong-Poi H. Angiotensinconverting enzyme 2 protects from severe acute lung failure[J]. Nature,2005,436(7047):112-116.

[17]Perlot T,Penninger J M. ACE2–From the renin–angiotensin system to gut microbiota and malnutrition[J]. Microbes Infect,2013,15(13):866-873.

[18]Han D P,Penn-Nicholson A,Cho M W. Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor[J].Virology,2006,350(1):15-25.

[19]Cui J,Li F,Shi Z L. Origin and evolution of pathogenic coronaviruses[J]. Nat Rev Microbiol,2019,17(3):181-192.

[20]Xu X,Chen P,Wang J,Feng J,Zhou H,Li X,Zhong W,Hao P. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission[J]. Sci China Life Sci,2020,63(3):457-460.

[21]Ren L L,Wang Y M,Wu Z Q,Xiang Z C,Guo L,Xu T,Jiang Y Z,Xiong Y,Li Y J,Li X W. Identification of a novel coronavirus causing severe pneumonia in human:a descriptive study[J]. Chin Med J,2020,133(9):1015-1024.

[22]Letko M, Munster V. Functional assessment of cell entry and receptor usage for lineage Bβ-coronaviruses,including 2019-nCoV[J]. Nat Microbiol,2020,5(4):562-569.

[23]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 H D,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 Q J,Deng F,Liu L L,Yan B,Zhan F X,Wang Y Y,Xiao G F,Shi Z L. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin[J]. BioRxiv,2020.DOI:10.1101/2020.01.22.914952

[24]Wan Y, Shang J, Graham R, Baric R S, Li F.Receptor recognition by the novel coronavirus from Wuhan:an analysis based on decade-long structural studies of SARS coronavirus[J]. J Virol,2020,94(7):1-9.

[25]Hoffmann M,Kleine-Weber H,Krüger N,Mueller M A, Drosten C, P?hlmann S. The novel coronavirus2019(2019-nCoV)uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells[J]. BioRxiv, 2020. DOI:10.1101/2020.01.31.929042

[26]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,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 2019 Novel Coronavirus in hACE2 Transgenic Mice[J]. Nature,2020,583(7818):830-833.

[27]Huang C,Wang Y,Li X,Ren L,Zhao J,Hu Y,Zhang L,Fan G,Xu J,Gu X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan,China[J]. Lancet,2020,395(10223):497-506.

[28]Guan W J,Ni Z Y,Hu Y,Liang W H,Ou C Q,He J X, Liu L, Shan H, Lei C L, Hui D S. Clinical characteristics of 2019 novel coronavirus infection in China[J]. New Engl J Med, 2020, 1-13. DOI:10.1056/NEJMoa2002032

[29]侯涛.武汉金银潭医生前线手记:新型冠状病毒肺炎临床特征初探[EB/OL]. 2020-1-29[2020-10-26].http://news. medlive. cn/all/info-news/show-165664_97.html

[30]Lei C,Fu W,Qian K,Li T,Zhang S,Ding M,Hu S.Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig[J]. BioRxiv, 2020. DOI:10.1128/JVI.01283-20

[31]An P,Chen H B,Jiang X D,Su J,Xiao Y,Ding Y J,Ren H X,Ji M Y,Chen Y F,Chen W,Lv X G,Shen L,Chen M K,Li J,Yin A N,Kang J,Liu S Z,Tan W,Wu L L,Dong W G,Cao J W,Zhou Z Y,Tan S Y,Chen G Z,Zhou J,Yang Y N,Yu H G. Clinical features of 2019 novel coronavirus pneumonia presented gastrointestinal symptoms but without fever onset[J].Lancet,2020-2-2[2020-10-26]. https://ssrn. com/abstract=3532530

[32]Liu K,Fang Y Y,Deng Y,Liu W,Wang M F,Ma J P,Xiao W,Wang Y N,Zhong M H,Li C H. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province[J]. Chin Med J,2020,133(9):1025-1031.

[33]Chen N,Zhou M,Dong X,Qu J,Gong F,Han Y,Qiu Y,Wang J,Liu Y,Wei Y. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan,China:a descriptive study[J]. Lancet,2020,395(10223):507-513.

[34]Wang D,Hu B,Hu C,Zhu F,Liu X,Zhang J,Wang B,Xiang H,Cheng Z,Xiong Y. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan,China[J]. JAMA,2020,323(11):1061-1069.

[35]Guan W J,Ni Z Y,Hu Y,Liang W H,Ou C Q,He J X, Liu L, Shan H, Lei C L, Hui D S. Clinical characteristics of 2019 novel coronavirus infection in China[J]. New Engl J Med, 2020, 1-13. DOI:10.1056/NEJMoa2002032

[36]Dales N A,Gould A E,Brown J A,Calderwood E F,Guan B,Minor C A,Gavin J M,Hales P,Kaushik V K,Stewart M. Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase(ACE2)inhibitors[J]. J Am Chem Soc,2002,124(40):11852-11853.

[37]Huang L,Sexton D J,Skogerson K,Devlin M,Smith R,Sanyal I,Parry T,Kent R,Enright J,Wu Q L,Conley G, DeOliveira D, Morganelli L, Ducar M,Wescott C R,Ladner R C. Novel peptide inhibitors of angiotensin-converting enzyme 2[J]. J Biol Chem,2003,278(18):15532-15540.

[38]Cavanagh D. Severe acute respiratory syndrome vaccine development:experiences of vaccination against avian infectious bronchitis coronavirus[J]. Avian Pathol,2003,32(6):567-582.

基本信息:

DOI:10.13242/j.cnki.bingduxuebao.003824

中图分类号:R373

引用信息:

[1]郭建淑,张燕,孙学春等.新型冠状病毒受体血管紧张素转换酶2的研究进展[J].病毒学报,2020,36(06):1165-1170.DOI:10.13242/j.cnki.bingduxuebao.003824.

基金信息:

检 索 高级检索

引用

GB/T 7714-2015 格式引文
MLA格式引文
APA格式引文