Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target

Intensive Care Medicine

Volumn 46, Issue 4, 2020, Pages 586-590

  Zhang, Haibo ^a,b,c   Penninger, Josef M ^d,e   Li, Yimin ^c   Zhong, Nanshan ^c   Slutsky, Arthur S ^a,b,c  

^a ST MICHAEL'S HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c GUANGZHOU MEDICAL UNIVERSITY   (China)

^d UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^e ERICH SCHMID INSTITUTE OF MATERIALS SCIENCE   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOTENSIN CONVERTING ENZYME 2; ANGIOTENSIN CONVERTING ENZYME 2 RECEPTOR; RECEPTOR; UNCLASSIFIED DRUG; VIRUS SPIKE PROTEIN; VIRUS VACCINE; CORONAVIRUS SPIKE GLYCOPROTEIN; DIPEPTIDYL CARBOXYPEPTIDASE; VIRUS ENVELOPE PROTEIN; VIRUS RECEPTOR; VIRUS RNA;

ARTICLE; CHINA; CORONAVIRUS DISEASE 2019; ENZYME ACTIVITY; HUMAN; INTERMEDIATE HOST; LUNG ALVEOLUS EPITHELIUM CELL; NONHUMAN; PHYLOGENY; PROTEIN EXPRESSION; PROTEIN FUNCTION; RECEPTOR AFFINITY; RECEPTOR BINDING; RECEPTOR BLOCKING; SARS CORONAVIRUS; SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2; TARGET CELL; VACCINE PRODUCTION; VIRUS CELL INTERACTION; VIRUS ENTRY; VIRUS PATHOGENESIS; VIRUS REPLICATION; ADULT RESPIRATORY DISTRESS SYNDROME; BETACORONAVIRUS; COMPLICATION; ENZYMOLOGY; METABOLISM; SEVERE ACUTE RESPIRATORY SYNDROME; VIROLOGY;

ALVEOLAR EPITHELIAL CELLS; BETACORONAVIRUS; HUMANS; PEPTIDYL-DIPEPTIDASE A; RECEPTORS, VIRUS; RESPIRATORY DISTRESS SYNDROME, ADULT; RNA, VIRAL; SEVERE ACUTE RESPIRATORY SYNDROME; SPIKE GLYCOPROTEIN, CORONAVIRUS; VIRAL ENVELOPE PROTEINS;

EID: 85081557718     PISSN: 03424642     EISSN: 14321238     Source Type: Journal    
DOI: 10.1007/s00134-020-05985-9     Document Type: Article

References (35)

1. https://www.clinicaltrialsarena.com/news/company-news/gilead-coronavirus-remdesivir-trial/
2. Li G, De Clercq E (2020) Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 10.1038/d41573-020-00016-0
3. 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 WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 10.1016/s0140-6736(20)30251-8
4. Wan Y, Shang J, Graham R, Baric RS, Li F (2020) Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol. 10.1128/jvi.00127-20
5. https://www.nature.com/articles/d41586-020-00364-2
6. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, Zhong W, Hao P (2020) Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its Spike protein for risk of human transmission. Sci China Life Sci. 10.1007/s11427-020-1637-5
7. Li F, Li W, Farzan M, Harrison SC (2005) Structure of SARS coronavirus Spike receptor-binding domain complexed with receptor. Science 309:1864–1868
8. Wu KL, Peng GQ, Wilken M, Geraghty RJ, Li F (2012) Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. J Biol Chem 287:8904–8911
9. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–454
10. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM (2005) A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat Med 11:875–879
11. Yang XH, Deng W, Tong Z, Liu YX, Zhang LF, Zhu H, Gao H, Huang L, Liu YL, Ma CM, Xu YF, Ding MX, Deng HK, Qin C (2007) Mice transgenic from human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comput Med 57(5):450–459
12. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penniger JM (2005) Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436:112–116
13. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 10.1038/s41586-020-2012-7
14. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W (2020) Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan COVID-19. 10.1101/2020.01.26.919985
15. Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dos-Santos AJ, da Costa J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM (2002) Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417(6891):822–828
16. Danilczyk U, Sarao R, Remy C, Benabbas C, Stange G, Richter A, Arya S, Pospisilik JA, Singer D, Camargo SM, Makrides V, Ramadan T, Verrey F, Wagner CA, Penninger JM (2006) Essential role for collectrin in renal amino acid transport. Nature 444(7122):1088–1091
17. Gu J, Gong E, Zhang B, Zheng J, Gao Z, Zhong Y, Zou W, Zhan J, Wang S, Xie Z, Zhuang H, Wu B, Zhong H, Shao H, Fang W, Gao D, Pei F, Li X, He Z, Xu D, Shi X, Anderson VM, Leong AS (2005) Multiple organ infection and the pathogenesis of SARS. J Exp Med 202(3):415–424
18. Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H, Shen H, Qiu L, Li Z, Geng J, Cai J, Han J, Li X, Kang W, Weng D, Liang P, Jiang S (2004) Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol 203:622–630
19. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H (2004) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus: a first step in understanding SARS pathogenesis. J Pathol 203:631–663
20. Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, Sigl V, Hanada T, Hanada R, Lipinski S, Wild B, Camargo SM, Singer D, Richter A, Kuba K, Fukamizu A, Schreiber S, Clevers H, Verrey F, Rosenstiel P, Penninger JM (2012) ACE2 links amino acid malnutrition to microbial ecology andf intestinal inflammation. Nature 487(7408):477–481
21. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 10.1001/jama.2020.1585
22. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 10.1016/S0140-6736(20)30183-5
23. Guan W, Ni Z, Hu Y, Liang W, Ou C, He H, Liu L, Shan H, Lei C, Hui DSC, Du B, Li L, Zeng G, Yuen KY, Chen R, Tang C, Wang T, Chen P, Xiang J, Li S, Wang J, Liang Z, Peng Y, Wei L, Liu Y, Hu Y, Peng P, Wang J, Liu J, Chen Z, Li G, Zheng Z, Qiu S, Luo J, Ye C, Zhu S, Zhong N (2020) Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv. 10.1101/2020.02.06.20020974
24. https://www.cdc.gov/coronavirus/2019-ncov/about/transmission.html
25. Hoffmann M, Kleine-Weber H, Krüger N, Müller M, Drosten C, Pöhlmann S (2020) The novel coronavirus 2019 (COVID-19) uses the SARS-1 coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv. 10.1101/2020.01.31.929042
26. Glowacka I, Bertram S, Muller MA, Allen P, Soilleux E, Pfefferle S, Steffen I, Tsegaye TS, He Y, Gnirss K, Niemeyer D, Schneider H, Drosten C, Pöhlmann S (2011) Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus Spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol 85:4122–4134
27. Iwata-Yoshikawa N, Okamura T, Shimizu Y, Hasegawa H, Takeda M, Nagata N (2019) TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. J Virol. 10.1128/jvi.01815-18
28. Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S (2012) Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol 86:6537–6654
29. Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R Jr, Nunneley JW, Barnard D, Pöhlmann S, McKerrow JH, Renslo AR, Simmons G (2015) Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res 116:76–84
30. Yu L, Yuan K, Phuong HT, Park BM, Kim SH (2016) Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor. Peptides 86:33–41
31. Zhang R, Pan Y, Fanelli V, Wu S, Luo AA, Islam D, Han B, Mao P, Ghazarian M, Zeng W, Spieth PM, Wnag D, Khang J, Mo H, Liu X, Uhlig S, Liu M, Laffey J, Slutsky AS, Li Y, Zhang H (2015) Mechanical stress and the induction of lung fibrosis via the midkine signaling pathway. Am J Respir Crit Care Med 192:315–323
32. Wosten-van Asperen RM, Lutter R, Specht PA, Moll GN, van Woensel JB, van der Loos CM, van Goor H, Kamilic J, Florquin S, Bos AP (2011) Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist. J Pathol 225:618–627
33. Haschke M, Schuster M, Poglitsch M, Loibner H, Salzberg M, Bruggisser M, Penninger J, Krahenbuhl S (2013) Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clin Pharmacokinet 52:783–792
34. Khan A, Benthin C, Zeno B, Albertson TE, Boyd J, Christie JD, Hall R, Poirier G, Ronco JJ, Tidswell M et al (2017) A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit Care 21:234
35. Zhang H, Baker A (2017) Recombinant human ACE2: acing out angiotensin II in ARDS therapy. Crit Care 21:305