Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target
Haibo Zhang, Josef M Penninger, Yimin Li, Nanshan Zhong, Arthur S Slutsky
Intensive Care Medicine, doi:10.1007/s00134-020-05985-9
A novel infectious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in Wuhan, China, in December 2019. The disease (COVID-19) spread rapidly, reaching epidemic proportions in China, and has been found in 27 other countries. As of February 27, 2020, over 82,000 cases of COVID-19 were reported, with > 2800 deaths. No specific therapeutics are available, and current management includes travel restrictions, patient isolation, and supportive medical care. There are a number of pharmaceuticals already being tested [1, 2], but a better understanding of the underlying pathobiology is required. In this context, this article will briefly review the rationale for angiotensin-converting enzyme 2 (ACE2) receptor as a specific target.
Conflicts of interest Josef Penninger is the founder and a shareholder of Apeiron, the company that makes rhACE2. Arthur Slutsky has been a paid consultant for Apeiron. No other conflicts of interested have been reported.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by-nc/4.0/ .
References
Crackower, Sarao, Oudit, Yagil, Kozieradzki et al., Angiotensin-converting enzyme 2 is an essential regulator of heart function, Nature
Danilczyk, Sarao, Remy, Benabbas, Stange et al., Essential role for collectrin in renal amino acid transport, Nature
Ding, He, Zhang, Huang, Hou et al., Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways, J Pathol
Glowacka, Bertram, Muller, Allen, Soilleux et al., 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
Gu, Gong, Zhang, Zheng, Gao et al., Multiple organ infection and the pathogenesis of SARS, J Exp Med
Hamming, Timens, Bulthuis, Lely, Navis et al., Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus: a first step in understanding SARS pathogenesis, J Pathol
Haschke, Schuster, Poglitsch, Loibner, Salzberg et al., Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects, Clin Pharmacokinet
Hashimoto, Perlot, Rehman, Trichereau, Ishiguro et al., ACE2 links amino acid malnutrition to microbial ecology andf intestinal inflammation, Nature
Hoffmann, Kleine-Weber, Krüger, Müller, Drosten et al., The novel coronavirus 2019 (COVID-19) uses the SARS-1 coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells, bioRxiv,
doi:10.1101/2020.01.31.929042Imai, Kuba, Rao, Huan, Guo et al., Angiotensin-converting enzyme 2 protects from severe acute lung failure, Nature
Iwata-Yoshikawa, Okamura, Shimizu, Hasegawa, Takeda et al., TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection, J Virol,
doi:10.1128/jvi.01815-18Kawase, Shirato, Van Der Hoek, Taguchi, Matsuyama, Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry, J Virol
Khan, Benthin, Zeno, Albertson, Boyd et al., A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome, Crit Care
Kuba, Imai, Rao, Gao, Guo et al., A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirusinduced lung injury, Nat Med
Li, Li, Farzan, Harrison, Structure of SARS coronavirus Spike receptor-binding domain complexed with receptor, Science
Li, Moore, Vasilieva, Sui, Wong et al., Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus, Nature
Lu, Zhao, Li, Niu, Yang et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding, Lancet,
doi:10.1016/s0140-6736(20)30251-8Wan, Shang, Graham, Baric, Li, Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS, J Virol,
doi:10.1128/jvi.00127-20Wang, Hu, Hu, Zhu, Liu et al., Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA,
doi:10.1001/jama.2020.1585Wosten-Van Asperen, Lutter, Specht, Moll, Van Woensel et al., 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
Wu, Peng, Wilken, Geraghty, Li, Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus, J Biol Chem
Xu, Chen, Wang, Feng, Zhou et al., 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,
doi:10.1007/s11427-020-1637-5Yang, Deng, Tong, Liu, Zhang et al., Mice transgenic from human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection, Comput Med
Yu, Yuan, Phuong, Park, Kim, Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor, Peptides
Zhang, Baker, Recombinant human ACE2: acing out angiotensin II in ARDS therapy, Crit Care
Zhang, Pan, Fanelli, Wu, Luo et al., Mechanical stress and the induction of lung fibrosis via the midkine signaling pathway, Am J Respir Crit Care Med
Zhao, Zhao, Wang, Zhou, Ma et al., Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan COVID-19,
doi:10.1101/2020.01.26.919985Zhou, Vedantham, Lu, Agudelo, Carrion R Jr et al., Protease inhibitors targeting coronavirus and filovirus entry, Antiviral Res
Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature,
doi:10.1038/s41586-020-2012-7DOI record:
{
"DOI": "10.1007/s00134-020-05985-9",
"ISSN": [
"0342-4642",
"1432-1238"
],
"URL": "http://dx.doi.org/10.1007/s00134-020-05985-9",
"alternative-id": [
"5985"
],
"assertion": [
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "Received",
"name": "received",
"order": 1,
"value": "17 February 2020"
},
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "Accepted",
"name": "accepted",
"order": 2,
"value": "20 February 2020"
},
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "First Online",
"name": "first_online",
"order": 3,
"value": "3 March 2020"
},
{
"group": {
"label": "Compliance with ethical standards",
"name": "EthicsHeading"
},
"name": "Ethics",
"order": 1
},
{
"group": {
"label": "Conflicts of interest",
"name": "EthicsHeading"
},
"name": "Ethics",
"order": 2,
"value": "Josef Penninger is the founder and a shareholder of Apeiron, the company that makes rhACE2. Arthur Slutsky has been a paid consultant for Apeiron. No other conflicts of interested have been reported."
}
],
"author": [
{
"ORCID": "https://orcid.org/0000-0002-1714-3038",
"affiliation": [],
"authenticated-orcid": false,
"family": "Zhang",
"given": "Haibo",
"sequence": "first"
},
{
"affiliation": [],
"family": "Penninger",
"given": "Josef M.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Li",
"given": "Yimin",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Zhong",
"given": "Nanshan",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Slutsky",
"given": "Arthur S.",
"sequence": "additional"
}
],
"container-title": "Intensive Care Medicine",
"container-title-short": "Intensive Care Med",
"content-domain": {
"crossmark-restriction": false,
"domain": [
"link.springer.com"
]
},
"created": {
"date-parts": [
[
2020,
3,
3
]
],
"date-time": "2020-03-03T10:03:06Z",
"timestamp": 1583229786000
},
"deposited": {
"date-parts": [
[
2021,
3,
3
]
],
"date-time": "2021-03-03T00:11:45Z",
"timestamp": 1614730305000
},
"funder": [
{
"DOI": "10.13039/501100000028",
"award": [
"FDN143285"
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100000028",
"id-type": "DOI"
}
],
"name": "Institute of Circulatory and Respiratory Health"
},
{
"DOI": "10.13039/100000001",
"award": [
"81270125",
"81490530",
"2018GZR0201002"
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100000001",
"id-type": "DOI"
}
],
"name": "\"Natural Science Foundation of China\""
}
],
"indexed": {
"date-parts": [
[
2025,
2,
21
]
],
"date-time": "2025-02-21T03:22:58Z",
"timestamp": 1740108178552,
"version": "3.37.3"
},
"is-referenced-by-count": 1945,
"issue": "4",
"issued": {
"date-parts": [
[
2020,
3,
3
]
]
},
"journal-issue": {
"issue": "4",
"published-print": {
"date-parts": [
[
2020,
4
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://creativecommons.org/licenses/by-nc/4.0",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
3,
3
]
],
"date-time": "2020-03-03T00:00:00Z",
"timestamp": 1583193600000
}
},
{
"URL": "https://creativecommons.org/licenses/by-nc/4.0",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
3,
3
]
],
"date-time": "2020-03-03T00:00:00Z",
"timestamp": 1583193600000
}
}
],
"link": [
{
"URL": "http://link.springer.com/content/pdf/10.1007/s00134-020-05985-9.pdf",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "http://link.springer.com/article/10.1007/s00134-020-05985-9/fulltext.html",
"content-type": "text/html",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "http://link.springer.com/content/pdf/10.1007/s00134-020-05985-9.pdf",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "297",
"original-title": [],
"page": "586-590",
"prefix": "10.1007",
"published": {
"date-parts": [
[
2020,
3,
3
]
]
},
"published-online": {
"date-parts": [
[
2020,
3,
3
]
]
},
"published-print": {
"date-parts": [
[
2020,
4
]
]
},
"publisher": "Springer Science and Business Media LLC",
"reference": [
{
"key": "5985_CR1",
"unstructured": "https://www.clinicaltrialsarena.com/news/company-news/gilead-coronavirus-remdesivir-trial/"
},
{
"DOI": "10.1038/d41573-020-00016-0",
"author": "G Li",
"doi-asserted-by": "publisher",
"journal-title": "Nat Rev Drug Discov",
"key": "5985_CR2",
"unstructured": "Li G, De Clercq E (2020) Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. https://doi.org/10.1038/d41573-020-00016-0",
"year": "2020"
},
{
"DOI": "10.1016/s0140-6736(20)30251-8",
"author": "R Lu",
"doi-asserted-by": "publisher",
"journal-title": "Lancet",
"key": "5985_CR3",
"unstructured": "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. https://doi.org/10.1016/s0140-6736(20)30251-8",
"year": "2020"
},
{
"DOI": "10.1128/jvi.00127-20",
"author": "Y Wan",
"doi-asserted-by": "publisher",
"journal-title": "J Virol",
"key": "5985_CR4",
"unstructured": "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. https://doi.org/10.1128/jvi.00127-20",
"year": "2020"
},
{
"key": "5985_CR5",
"unstructured": "https://www.nature.com/articles/d41586-020-00364-2"
},
{
"DOI": "10.1007/s11427-020-1637-5",
"author": "X Xu",
"doi-asserted-by": "publisher",
"journal-title": "Sci China Life Sci",
"key": "5985_CR6",
"unstructured": "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. https://doi.org/10.1007/s11427-020-1637-5",
"year": "2020"
},
{
"DOI": "10.1126/science.1116480",
"author": "F Li",
"doi-asserted-by": "publisher",
"first-page": "1864",
"journal-title": "Science",
"key": "5985_CR7",
"unstructured": "Li F, Li W, Farzan M, Harrison SC (2005) Structure of SARS coronavirus Spike receptor-binding domain complexed with receptor. Science 309:1864–1868",
"volume": "309",
"year": "2005"
},
{
"DOI": "10.1074/jbc.M111.325803",
"author": "KL Wu",
"doi-asserted-by": "publisher",
"first-page": "8904",
"journal-title": "J Biol Chem",
"key": "5985_CR8",
"unstructured": "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",
"volume": "287",
"year": "2012"
},
{
"DOI": "10.1038/nature02145",
"author": "W Li",
"doi-asserted-by": "publisher",
"first-page": "450",
"journal-title": "Nature",
"key": "5985_CR9",
"unstructured": "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",
"volume": "426",
"year": "2003"
},
{
"DOI": "10.1038/nm1267",
"author": "K Kuba",
"doi-asserted-by": "publisher",
"first-page": "875",
"journal-title": "Nat Med",
"key": "5985_CR10",
"unstructured": "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",
"volume": "11",
"year": "2005"
},
{
"author": "XH Yang",
"first-page": "450",
"issue": "5",
"journal-title": "Comput Med",
"key": "5985_CR11",
"unstructured": "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",
"volume": "57",
"year": "2007"
},
{
"DOI": "10.1038/nature03712",
"author": "Y Imai",
"doi-asserted-by": "publisher",
"first-page": "112",
"journal-title": "Nature",
"key": "5985_CR12",
"unstructured": "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",
"volume": "436",
"year": "2005"
},
{
"DOI": "10.1038/s41586-020-2012-7",
"author": "P Zhou",
"doi-asserted-by": "publisher",
"journal-title": "Nature",
"key": "5985_CR13",
"unstructured": "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. https://doi.org/10.1038/s41586-020-2012-7",
"year": "2020"
},
{
"DOI": "10.1101/2020.01.26.919985",
"doi-asserted-by": "publisher",
"key": "5985_CR14",
"unstructured": "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. https://doi.org/10.1101/2020.01.26.919985"
},
{
"DOI": "10.1038/nature00786",
"author": "MA Crackower",
"doi-asserted-by": "publisher",
"first-page": "822",
"issue": "6891",
"journal-title": "Nature",
"key": "5985_CR15",
"unstructured": "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",
"volume": "417",
"year": "2002"
},
{
"DOI": "10.1038/nature05475",
"author": "U Danilczyk",
"doi-asserted-by": "publisher",
"first-page": "1088",
"issue": "7122",
"journal-title": "Nature",
"key": "5985_CR16",
"unstructured": "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",
"volume": "444",
"year": "2006"
},
{
"DOI": "10.1084/jem.20050828",
"author": "J Gu",
"doi-asserted-by": "publisher",
"first-page": "415",
"issue": "3",
"journal-title": "J Exp Med",
"key": "5985_CR17",
"unstructured": "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",
"volume": "202",
"year": "2005"
},
{
"DOI": "10.1002/path.1560",
"author": "Y Ding",
"doi-asserted-by": "publisher",
"first-page": "622",
"journal-title": "J Pathol",
"key": "5985_CR18",
"unstructured": "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",
"volume": "203",
"year": "2004"
},
{
"DOI": "10.1002/path.1570",
"author": "I Hamming",
"doi-asserted-by": "publisher",
"first-page": "631",
"journal-title": "J Pathol",
"key": "5985_CR19",
"unstructured": "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",
"volume": "203",
"year": "2004"
},
{
"DOI": "10.1038/nature11228",
"author": "T Hashimoto",
"doi-asserted-by": "publisher",
"first-page": "477",
"issue": "7408",
"journal-title": "Nature",
"key": "5985_CR20",
"unstructured": "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",
"volume": "487",
"year": "2012"
},
{
"DOI": "10.1001/jama.2020.1585",
"author": "D Wang",
"doi-asserted-by": "publisher",
"journal-title": "JAMA",
"key": "5985_CR21",
"unstructured": "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. https://doi.org/10.1001/jama.2020.1585",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)30183-5",
"author": "C Huang",
"doi-asserted-by": "publisher",
"journal-title": "Lancet",
"key": "5985_CR22",
"unstructured": "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. https://doi.org/10.1016/S0140-6736(20)30183-5",
"year": "2020"
},
{
"DOI": "10.1101/2020.02.06.20020974",
"author": "W Guan",
"doi-asserted-by": "publisher",
"journal-title": "medRxiv",
"key": "5985_CR23",
"unstructured": "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. https://doi.org/10.1101/2020.02.06.20020974",
"year": "2020"
},
{
"key": "5985_CR24",
"unstructured": "https://www.cdc.gov/coronavirus/2019-ncov/about/transmission.html"
},
{
"DOI": "10.1101/2020.01.31.929042",
"author": "M Hoffmann",
"doi-asserted-by": "publisher",
"journal-title": "bioRxiv",
"key": "5985_CR25",
"unstructured": "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. https://doi.org/10.1101/2020.01.31.929042",
"year": "2020"
},
{
"DOI": "10.1128/JVI.02232-10",
"author": "I Glowacka",
"doi-asserted-by": "publisher",
"first-page": "4122",
"journal-title": "J Virol",
"key": "5985_CR26",
"unstructured": "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",
"volume": "85",
"year": "2011"
},
{
"DOI": "10.1128/jvi.01815-18",
"author": "N Iwata-Yoshikawa",
"doi-asserted-by": "publisher",
"journal-title": "J Virol",
"key": "5985_CR27",
"unstructured": "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. https://doi.org/10.1128/jvi.01815-18",
"year": "2019"
},
{
"DOI": "10.1128/JVI.00094-12",
"author": "M Kawase",
"doi-asserted-by": "publisher",
"first-page": "6537",
"journal-title": "J Virol",
"key": "5985_CR28",
"unstructured": "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",
"volume": "86",
"year": "2012"
},
{
"DOI": "10.1016/j.antiviral.2015.01.011",
"author": "Y Zhou",
"doi-asserted-by": "publisher",
"first-page": "76",
"journal-title": "Antiviral Res",
"key": "5985_CR29",
"unstructured": "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",
"volume": "116",
"year": "2015"
},
{
"DOI": "10.1016/j.peptides.2016.09.009",
"author": "L Yu",
"doi-asserted-by": "publisher",
"first-page": "33",
"journal-title": "Peptides",
"key": "5985_CR30",
"unstructured": "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",
"volume": "86",
"year": "2016"
},
{
"DOI": "10.1164/rccm.201412-2326OC",
"author": "R Zhang",
"doi-asserted-by": "publisher",
"first-page": "315",
"journal-title": "Am J Respir Crit Care Med",
"key": "5985_CR31",
"unstructured": "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",
"volume": "192",
"year": "2015"
},
{
"DOI": "10.1002/path.2987",
"author": "RM Wosten-van Asperen",
"doi-asserted-by": "publisher",
"first-page": "618",
"journal-title": "J Pathol",
"key": "5985_CR32",
"unstructured": "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",
"volume": "225",
"year": "2011"
},
{
"DOI": "10.1007/s40262-013-0072-7",
"author": "M Haschke",
"doi-asserted-by": "publisher",
"first-page": "783",
"journal-title": "Clin Pharmacokinet",
"key": "5985_CR33",
"unstructured": "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",
"volume": "52",
"year": "2013"
},
{
"DOI": "10.1186/s13054-017-1823-x",
"author": "A Khan",
"doi-asserted-by": "publisher",
"first-page": "234",
"journal-title": "Crit Care",
"key": "5985_CR34",
"unstructured": "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",
"volume": "21",
"year": "2017"
},
{
"DOI": "10.1186/s13054-017-1882-z",
"author": "H Zhang",
"doi-asserted-by": "publisher",
"first-page": "305",
"journal-title": "Crit Care",
"key": "5985_CR35",
"unstructured": "Zhang H, Baker A (2017) Recombinant human ACE2: acing out angiotensin II in ARDS therapy. Crit Care 21:305",
"volume": "21",
"year": "2017"
}
],
"reference-count": 35,
"references-count": 35,
"relation": {},
"resource": {
"primary": {
"URL": "http://link.springer.com/10.1007/s00134-020-05985-9"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target",
"type": "journal-article",
"update-policy": "https://doi.org/10.1007/springer_crossmark_policy",
"volume": "46"
}
