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Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence
Alpha-1-antitrypsin (AAT), a serine protease inhibitor (serpin), is increasingly recognized to inhibit SARS-CoV-2 infection and counter many of the pathogenic mechanisms of COVID-19. Herein, we reviewed the epidemiologic evidence, the molecular mechanisms, and the clinical evidence that support this...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317171/ https://www.ncbi.nlm.nih.gov/pubmed/37294003 http://dx.doi.org/10.1042/BST20230078 |
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author | Bai, Xiyuan Schountz, Tony Buckle, Ashley M. Talbert, Janet L. Sandhaus, Robert A. Chan, Edward D. |
author_facet | Bai, Xiyuan Schountz, Tony Buckle, Ashley M. Talbert, Janet L. Sandhaus, Robert A. Chan, Edward D. |
author_sort | Bai, Xiyuan |
collection | PubMed |
description | Alpha-1-antitrypsin (AAT), a serine protease inhibitor (serpin), is increasingly recognized to inhibit SARS-CoV-2 infection and counter many of the pathogenic mechanisms of COVID-19. Herein, we reviewed the epidemiologic evidence, the molecular mechanisms, and the clinical evidence that support this paradigm. As background to our discussion, we first examined the basic mechanism of SARS-CoV-2 infection and contend that despite the availability of vaccines and anti-viral agents, COVID-19 remains problematic due to viral evolution. We next underscored that measures to prevent severe COVID-19 currently exists but teeters on a balance and that current treatment for severe COVID-19 remains grossly suboptimal. We then reviewed the epidemiologic and clinical evidence that AAT deficiency increases risk of COVID-19 infection and of more severe disease, and the experimental evidence that AAT inhibits cell surface transmembrane protease 2 (TMPRSS2) — a host serine protease required for SARS-CoV-2 entry into cells — and that this inhibition may be augmented by heparin. We also elaborated on the panoply of other activities of AAT (and heparin) that could mitigate severity of COVID-19. Finally, we evaluated the available clinical evidence for AAT treatment of COVID-19. |
format | Online Article Text |
id | pubmed-10317171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103171712023-07-04 Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence Bai, Xiyuan Schountz, Tony Buckle, Ashley M. Talbert, Janet L. Sandhaus, Robert A. Chan, Edward D. Biochem Soc Trans Review Articles Alpha-1-antitrypsin (AAT), a serine protease inhibitor (serpin), is increasingly recognized to inhibit SARS-CoV-2 infection and counter many of the pathogenic mechanisms of COVID-19. Herein, we reviewed the epidemiologic evidence, the molecular mechanisms, and the clinical evidence that support this paradigm. As background to our discussion, we first examined the basic mechanism of SARS-CoV-2 infection and contend that despite the availability of vaccines and anti-viral agents, COVID-19 remains problematic due to viral evolution. We next underscored that measures to prevent severe COVID-19 currently exists but teeters on a balance and that current treatment for severe COVID-19 remains grossly suboptimal. We then reviewed the epidemiologic and clinical evidence that AAT deficiency increases risk of COVID-19 infection and of more severe disease, and the experimental evidence that AAT inhibits cell surface transmembrane protease 2 (TMPRSS2) — a host serine protease required for SARS-CoV-2 entry into cells — and that this inhibition may be augmented by heparin. We also elaborated on the panoply of other activities of AAT (and heparin) that could mitigate severity of COVID-19. Finally, we evaluated the available clinical evidence for AAT treatment of COVID-19. Portland Press Ltd. 2023-06-28 2023-06-09 /pmc/articles/PMC10317171/ /pubmed/37294003 http://dx.doi.org/10.1042/BST20230078 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Articles Bai, Xiyuan Schountz, Tony Buckle, Ashley M. Talbert, Janet L. Sandhaus, Robert A. Chan, Edward D. Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence |
title | Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence |
title_full | Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence |
title_fullStr | Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence |
title_full_unstemmed | Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence |
title_short | Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence |
title_sort | alpha-1-antitrypsin antagonizes covid-19: a review of the epidemiology, molecular mechanisms, and clinical evidence |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317171/ https://www.ncbi.nlm.nih.gov/pubmed/37294003 http://dx.doi.org/10.1042/BST20230078 |
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