新型冠状病毒受体血管紧张素转换酶2及其相关干预药物

边经纬, 赵荣生, 翟所迪, 李子健

中国药学杂志 ›› 2020, Vol. 55 ›› Issue (10) : 761-766.

PDF(4716 KB)
中国药学杂志
PDF(4716 KB)
中国药学杂志 ›› 2020, Vol. 55 ›› Issue (10) : 761-766. DOI: 10.11669/cpj.2020.10.001
新冠疫情防控专栏

新型冠状病毒受体血管紧张素转换酶2及其相关干预药物

  • 边经纬1,2, 赵荣生1, 翟所迪1, 李子健1,2*
作者信息 +

Severe Acute Respiratory Syndrome Coronavirus 2 Receptor Angiotensin Converting Enzyme 2 and Its Related Intervention Drugs

  • BIAN Jing-wei1,2, ZHAO Rong-sheng1, ZHAI Suo-di1, LI Zi-jian1,2*
Author information +
文章历史 +

摘要

新型冠状病毒(SARS-CoV-2)引起的新型冠状病毒感染性疾病(COVID-19)在全球范围内暴发,对公共卫生安全构成了巨大威胁。血管紧张素转换酶2(ACE2)是SARS-CoV-2重要的功能受体,介导病毒侵入宿主细胞。因此,深入了解ACE2、其与病毒的关系及相关药物,对COVID-19预防和治疗研究具有重要意义。笔者从结构,表达和功能等方面总结ACE2和SARS-CoV-2最新研究进展,总结ACE2介导病毒侵入宿主细胞的机制及ACE2相关干预药物,为抗病毒的防预和治疗提供理论参考。

Abstract

The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world, which has posed a great threat to global public health security. Angiotensin converting enzyme 2 (ACE2) has been identified as the major functional receptor of SARS-CoV-2, which plays an essential role in mediating virus invasion into host cells. Thus, an in-depth understanding of the recent progress of ACE2, its relationship with the virus and related drugs is of great significance for the prevention and treatment of COVID-19. Here, from the aspects of structure, expression and function, this article reviews the latest research progress of ACE2 and SARS-CoV-2. Meanwhile, this article also summarizes the mechanism of ACE2-mediated virus invasion and ACE2-related drugs, which will provide theoretical reference for viral prevention and treatment.

关键词

新型冠状病毒 / 新型冠状病毒感染性疾病 / 血管紧张素转换酶2 / 肾素血管紧张素系统 / 药物

Key words

SARS-CoV-2 / COVID-19 / angiotensin-converting enzyme 2 / renin-angiotensin system / drugs

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用
边经纬, 赵荣生, 翟所迪, 李子健. 新型冠状病毒受体血管紧张素转换酶2及其相关干预药物[J]. 中国药学杂志, 2020, 55(10): 761-766 https://doi.org/10.11669/cpj.2020.10.001
BIAN Jing-wei, ZHAO Rong-sheng, ZHAI Suo-di, LI Zi-jian. Severe Acute Respiratory Syndrome Coronavirus 2 Receptor Angiotensin Converting Enzyme 2 and Its Related Intervention Drugs[J]. Chinese Pharmaceutical Journal, 2020, 55(10): 761-766 https://doi.org/10.11669/cpj.2020.10.001
中图分类号： R97   

参考文献

[1] WORLD HEALTH ORGANIZATION. Coronavirus disease 2019 (COVID-19) Situation Report [EB/OL]. WHO, 2020. [2020-04-02]. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.
[2] XU X, CHEN P, WANG J, et al. 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
[3] SU S, WONG G, SHI W, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses[J]. Trends Microbiol, 2016, 24(6):490-502.
[4] PEIRIS J S, LAI S T, POON L L, et al. Coronavirus as a possible cause of severe acute respiratory syndrome[J]. Lancet, 2003, 361(9366):1319-1325.
[5] OKBA N M, RAJ V S, HAAGMANS B L. Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches[J]. Curr Opin Virol, 2017, 23: 49-58.
[6] COUTARD B, VALLE C, DE LAMBALLERIE X, et al. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade[J]. Antiviral Res, 2020, 176: 104742.
[7] LI F. Structure, function, and evolution of coronavirus spike proteins[J]. Annu Rev Virol, 2016, 3(1):237-261.
[8] CRACKOWER M A, SARAO R, OUDIT G Y, et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function[J].Nature, 2002, 417(6891):822-828.
[9] WAN Y, SHANG J, GRAHAM R, et al. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS[J]. J Virol, 2020, 94 (7):e00127-20. DOI:10.1128/JVI.00127-20.
[10] WRAPP D, WANG N, CORBETT K S,et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation[J]. Science, 2020, 367 (6483):1260-1263.
[11] LAN J, GE J, YU J, et al. Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor[J]. Nature, 2020, DOI: 10.1038/s41586-020-2180-5.
[12] TIPNIS S R, HOOPER N M, HYDE R, et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase[J]. J Biol Chem, 2000, 275(43):33238-33243.
[13] PAZ O M, RIQUELME J A, GARCIA L, et al. Counter-regulatory renin-angiotensin system in cardiovascular disease[J]. Nat Rev Cardiol, 2020, 17(2):116-129.
[14] KUBA K, IMAI Y, PENNINGER J M. Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases[J]. Circ J, 2013, 77(2):301-308.
[15] DONOGHUE M, HSIEH F, BARONAS E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9[J]. Circ Res, 2000, 87(5):E1-9.
[16] ZHANG H, WADA J, HIDA K, et al. Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys[J]. J Biol Chem, 2001, 276(20):17132-17139.
[17] YAN R, ZHANG Y, LI Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 [J]. Science, 2020, 367 (6485):1444-1448.
[18] TIKELLIS C, JOHNSTON C I, FORBES J M, et al. Characterization of renal angiotensin-converting enzyme 2 in diabetic nephropathy[J]. Hypertension, 2003, 41(3):392-397.
[19] HAMMING I, TIMENS W, BULTHUIS M L, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis[J]. J Pathol, 2004, 203(2):631-637.
[20] ZOU X, CHEN K, ZOU J, et al. The single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to Wuhan 2019-nCoV infection[J]. Front Med, 2020, DOI: 10.1007/s11684-020-0754-0.
[21] HEURICH A, HOFMANN-WINKLER H, GIERER S, et al. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein[J]. J Virol, 2014, 88(2):1293-1307.
[22] HOFFMANN M, KLEINE-WEBER H, SCHROEDER S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically-proven protease inhibitor[J]. Cell, 2020, DOI: 10.1016/j.cell.2020.02.052.
[23] VICKERS C, HALES P, KAUSHIK V, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase[J]. J Biol Chem, 2002, 277(17):14838- 14843.
[24] SANTOS R, SAMPAIO W O, ALZAMORA A C, et al. 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.
[25] LI F, LI W, FARZAN M, et al. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor[J]. Science, 2005, 309(5742):1864-1868.
[26] KUBA K, IMAI Y, RAO S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury[J]. Nat Med, 2005, 11(8):875-879.
[27] INOUE Y, TANAKA N, TANAKA Y, et al. Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ACE2 with the cytoplasmic tail deleted[J]. J Virol, 2007, 81(16):8722-8729.
[28] WANG H, YANG P, LIU K, et al. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway[J]. Cell Res, 2008, 18(2):290-301.
[29] LIU Y, YANG Y, ZHANG C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury[J]. Sci China Life Sci, 2020, DOI: 10.1360/SSV-2020-0037.
[30] HUANG F, GUO J, ZOU Z, et al. Angiotensin Ⅱ plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients[J]. Nat Commun, 2014, 5(1):3595. DOI: 10.1038/ncomms4595.
[31] ZOU Z, YAN Y, SHU Y, et al. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections[J]. Nat Commun, 2014, 5(1):3594. DOI: 10.1038/ncomms4594.
[32] CALDEIRA D, ALARCAO J, VAZ-CARNEIRO A, et al. Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and Meta-analysis[J]. BMJ, 2012, 345: e4260.
[33] FERRARIO C M, JESSUP J, CHAPPELL M C, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin Ⅱ receptor blockers on cardiac angiotensin-converting enzyme 2[J]. Circulation, 2005, 111(20):2605-2010.
[34] OCARANZA M P, GODOY I, JALIL J E, et al. Enalapril attenuates downregulation of angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat[J]. Hypertension, 2006, 48(4):572-578.
[35] ISHIYAMA Y, GALLAGHER P E, AVERILL D B, et al. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin Ⅱ receptors[J]. Hypertension, 2004, 43(5):970-976.
[36] TIAN X, LI C, HUANG A, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody[J]. Emerg Microbes Infect, 2020, 9(1):382-385.
[37] BHATTACHARYA M, SHARMA A R, PATRA P, et al. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): immunoinformatics approach[J]. J Med Virol, 2020, DOI: 10.1002/jmv.25736.
[38] LIU W, MORSE J S, LALONDE T, et al. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV[J]. Chembiochem, 2020, 21(5):730-738.
[39] VINCENT M J, BERGERON E, BENJANNET S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread[J]. Virol J, 2005, 2: 69, DOI: 10.1186/1743-422X-2-69.
[40] COLSON P, ROLAIN J M, RAOULT D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2[J].Int J Antimicrob Agents, 2020: 105923, DOI: 10.1016/j.ijantimicag.2020.105923.
[41] YAO X, YE F, ZHANG M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[J]. Clin Infect Dis, 2020, DOI: 10.1093/cid/ciaa237.
[42] LIU J, CAO R, XU M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro[J]. Cell Discov, 2020, 6: 16, DOI: 10.1038/s41421-020-0156-0.
[43] WANG M, CAO R, ZHANG L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro[J]. Cell Res, 2020,30(3):269-271.
[44] LI H, TAN X C, JIANG D, et al. Research progress in coronavirus and its therapeutic drugs[J]. Chin Pharm J(中国药学杂志), 2020, 55 (4):284-292.
[45] ZHANG J S, MA X C, YU F, et al. Teicoplanin potently blocks the cell entry of 2019-nCoV[J]. BioRxiv, 2020. DOI:10.1101/2020.02.05.935387.
[46] SHEN L W, MAO H J, WU Y L, et al. TMPRSS2: a potential target for treatment of influenza virus and coronavirus infections[J]. Biochimie, 2017, 142: 1-10.
[47] LUCAS J M, HEINLEIN C, KIM T, et al. The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis[J]. Cancer Discov, 2014, 4(11):1310-1325.

基金

国家自然科学基金项目资助(91939301,81820108031);北京市自然科学基金项目资助(7172235)
PDF(4716 KB)

Accesses

Citation

Detail
段落导航
相关文章

/

〈 〉