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Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury

The recent emergence of coronavirus disease-2019 (COVID-19) as a pandemic affecting millions of individuals has raised great concern throughout the world, and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was identified as the causative agent for COVID-19. The multifunctional prot...

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Autores principales: Oz, Murat, Lorke, Dietrich Ernst
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier Masson SAS. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836742/
https://www.ncbi.nlm.nih.gov/pubmed/33461019
http://dx.doi.org/10.1016/j.biopha.2020.111193
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author Oz, Murat
Lorke, Dietrich Ernst
author_facet Oz, Murat
Lorke, Dietrich Ernst
author_sort Oz, Murat
collection PubMed
description The recent emergence of coronavirus disease-2019 (COVID-19) as a pandemic affecting millions of individuals has raised great concern throughout the world, and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was identified as the causative agent for COVID-19. The multifunctional protein angiotensin converting enzyme 2 (ACE2) is accepted as its primary target for entry into host cells. In its enzymatic function, ACE2, like its homologue ACE, regulates the renin-angiotensin system (RAS) critical for cardiovascular and renal homeostasis in mammals. Unlike ACE, however, ACE2 drives an alternative RAS pathway by degrading Ang-II and thus operates to balance RAS homeostasis in the context of hypertension, heart failure, and cardiovascular as well as renal complications of diabetes. Outside the RAS, ACE2 hydrolyzes key peptides, such as amyloid-β, apelin, and [des-Arg9]-bradykinin. In addition to its enzymatic functions, ACE2 is found to regulate intestinal amino acid homeostasis and the gut microbiome. Although the non-enzymatic function of ACE2 as the entry receptor for SARS-CoV-2 has been well established, the contribution of enzymatic functions of ACE2 to the pathogenesis of COVID-19-related lung injury has been a matter of debate. A complete understanding of this central enzyme may begin to explain the various symptoms and pathologies seen in SARS-CoV-2 infected individuals, and may aid in the development of novel treatments for COVID-19.
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spelling pubmed-78367422021-01-26 Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury Oz, Murat Lorke, Dietrich Ernst Biomed Pharmacother Review The recent emergence of coronavirus disease-2019 (COVID-19) as a pandemic affecting millions of individuals has raised great concern throughout the world, and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was identified as the causative agent for COVID-19. The multifunctional protein angiotensin converting enzyme 2 (ACE2) is accepted as its primary target for entry into host cells. In its enzymatic function, ACE2, like its homologue ACE, regulates the renin-angiotensin system (RAS) critical for cardiovascular and renal homeostasis in mammals. Unlike ACE, however, ACE2 drives an alternative RAS pathway by degrading Ang-II and thus operates to balance RAS homeostasis in the context of hypertension, heart failure, and cardiovascular as well as renal complications of diabetes. Outside the RAS, ACE2 hydrolyzes key peptides, such as amyloid-β, apelin, and [des-Arg9]-bradykinin. In addition to its enzymatic functions, ACE2 is found to regulate intestinal amino acid homeostasis and the gut microbiome. Although the non-enzymatic function of ACE2 as the entry receptor for SARS-CoV-2 has been well established, the contribution of enzymatic functions of ACE2 to the pathogenesis of COVID-19-related lung injury has been a matter of debate. A complete understanding of this central enzyme may begin to explain the various symptoms and pathologies seen in SARS-CoV-2 infected individuals, and may aid in the development of novel treatments for COVID-19. The Author(s). Published by Elsevier Masson SAS. 2021-04 2021-01-05 /pmc/articles/PMC7836742/ /pubmed/33461019 http://dx.doi.org/10.1016/j.biopha.2020.111193 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Review
Oz, Murat
Lorke, Dietrich Ernst
Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury
title Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury
title_full Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury
title_fullStr Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury
title_full_unstemmed Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury
title_short Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury
title_sort multifunctional angiotensin converting enzyme 2, the sars-cov-2 entry receptor, and critical appraisal of its role in acute lung injury
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836742/
https://www.ncbi.nlm.nih.gov/pubmed/33461019
http://dx.doi.org/10.1016/j.biopha.2020.111193
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