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Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2
We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death du...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181998/ https://www.ncbi.nlm.nih.gov/pubmed/32333836 http://dx.doi.org/10.1016/j.cell.2020.04.004 |
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author | Monteil, Vanessa Kwon, Hyesoo Prado, Patricia Hagelkrüys, Astrid Wimmer, Reiner A. Stahl, Martin Leopoldi, Alexandra Garreta, Elena Hurtado del Pozo, Carmen Prosper, Felipe Romero, Juan Pablo Wirnsberger, Gerald Zhang, Haibo Slutsky, Arthur S. Conder, Ryan Montserrat, Nuria Mirazimi, Ali Penninger, Josef M. |
author_facet | Monteil, Vanessa Kwon, Hyesoo Prado, Patricia Hagelkrüys, Astrid Wimmer, Reiner A. Stahl, Martin Leopoldi, Alexandra Garreta, Elena Hurtado del Pozo, Carmen Prosper, Felipe Romero, Juan Pablo Wirnsberger, Gerald Zhang, Haibo Slutsky, Arthur S. Conder, Ryan Montserrat, Nuria Mirazimi, Ali Penninger, Josef M. |
author_sort | Monteil, Vanessa |
collection | PubMed |
description | We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000–5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections. |
format | Online Article Text |
id | pubmed-7181998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71819982020-04-27 Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 Monteil, Vanessa Kwon, Hyesoo Prado, Patricia Hagelkrüys, Astrid Wimmer, Reiner A. Stahl, Martin Leopoldi, Alexandra Garreta, Elena Hurtado del Pozo, Carmen Prosper, Felipe Romero, Juan Pablo Wirnsberger, Gerald Zhang, Haibo Slutsky, Arthur S. Conder, Ryan Montserrat, Nuria Mirazimi, Ali Penninger, Josef M. Cell Article We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000–5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections. Elsevier Inc. 2020-05-14 2020-04-24 /pmc/articles/PMC7181998/ /pubmed/32333836 http://dx.doi.org/10.1016/j.cell.2020.04.004 Text en © 2020 Elsevier Inc. 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 | Article Monteil, Vanessa Kwon, Hyesoo Prado, Patricia Hagelkrüys, Astrid Wimmer, Reiner A. Stahl, Martin Leopoldi, Alexandra Garreta, Elena Hurtado del Pozo, Carmen Prosper, Felipe Romero, Juan Pablo Wirnsberger, Gerald Zhang, Haibo Slutsky, Arthur S. Conder, Ryan Montserrat, Nuria Mirazimi, Ali Penninger, Josef M. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 |
title | Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 |
title_full | Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 |
title_fullStr | Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 |
title_full_unstemmed | Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 |
title_short | Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 |
title_sort | inhibition of sars-cov-2 infections in engineered human tissues using clinical-grade soluble human ace2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181998/ https://www.ncbi.nlm.nih.gov/pubmed/32333836 http://dx.doi.org/10.1016/j.cell.2020.04.004 |
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