A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury
Open accessAbstract
During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world. A new coronavirus (SARS-CoV) was identified as the SARS pathogen, which triggered severe pneumonia and acute, often lethal, lung failure. Moreover, among infected individuals influenza such as the Spanish flu and the emergence of new respiratory disease viruses have caused high lethality resulting from acute lung failure. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses.
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ACE2 had been identified as the receptor for SARS-CoV and SARS-CoV-2.
“Importantly, ACE2 (angiotensin-converting enzyme 2) had been identified as the receptor for SARS-CoV 4,5 and SARS-CoV-2.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [4]
The AngII-AT1R axis is involved in the ARDS induced by SARS-CoV-2 infection, like SARS-CoV-1-induced ARDS in a mouse model.
“Therefore, it is likely that the AngII–AT1R axis is involved in the ARDS induced by SARS-CoV-2 infection (15), which is like SARS-CoV-1-induced ARDS in a mouse model (344).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [344]
SARS-CoV-2 infects cells through interactions between its spike (S) protein and the ACE2 protein on target cells.
“CoV-2 — like SARS-CoV — infects cells through interactions between its spike (S) protein and the ACE2 protein on target cells.”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [25]
The interaction between SARS-CoV-2 S protein and ACE2 requires cleavage of the S protein, likely by TMPRSS2, although other proteases such as Cathepsin B and L may also be involved.
“This interaction requires cleavage of the S protein, likely by the cell surface protease TMPRSS2, although other proteases (such as Cathepsin B and L, CTSB/CTSL) may also be involved (4-6, 22-25).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [25]
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- Authors
- 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, A. S., Liu, D., Qin, C., Jiang, C., & Penninger, J. M.
- Affiliations
- Institute of Molecular Biotechnology (AT)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Wake Forest University Health Sciences (US)
- St. Michael's Hospital (CA)
- Corresponding author
- Jiang, Chengyu
- ORCID
- Venue
- Nature Medicine
- Published
- 2005-07-10
- Volume
- 11
- Issue
- 8
- Pages
- 875-879
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC7095783
- OpenAlex
- W2091671824
- Cited by
- 3,445
- References
- 30
- Citations by year
- 2026: 28 · 2025: 55 · 2024: 136 · 2023: 223 · 2022: 391 · 2021: 875 · 2020: 1421 · 2019: 19 · 2018: 10 · 2017: 12 · 2016: 18 · 2015: 11 · 2014: 34 · 2013: 18 · 2012: 21
- FWCI
- 22.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30421003)
- Österreichischen Akademie der Wissenschaften
- Oesterreichische Nationalbank
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- angiotensin-converting enzyme 2, SARS-CoV, SARS, viral receptor, spike protein, acute lung injury, acute lung failure, renin-angiotensin system, viral pathogenesis, antiviral therapy, respiratory viruses
- MeSH terms
- Angiotensin-Converting Enzyme 2, Analysis of Variance, Animals, Carboxypeptidases, Immunohistochemistry, Peptidyl-Dipeptidase A, Lung Diseases, Membrane Glycoproteins, Viral Envelope Proteins, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice, Spike Glycoprotein, Coronavirus
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