Abstract |
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.
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Authors | Vanessa Monteil, Hyesoo Kwon, Patricia Prado, Astrid Hagelkrüys, Reiner A Wimmer, Martin Stahl, Alexandra Leopoldi, Elena Garreta, Carmen Hurtado Del Pozo, Felipe Prosper, Juan Pablo Romero, Gerald Wirnsberger, Haibo Zhang, Arthur S Slutsky, Ryan Conder, Nuria Montserrat, Ali Mirazimi, Josef M Penninger |
Journal | Cell
(Cell)
Vol. 181
Issue 4
Pg. 905-913.e7
(05 14 2020)
ISSN: 1097-4172 [Electronic] United States |
PMID | 32333836
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
- Receptors, Virus
- Recombinant Proteins
- Spike Glycoprotein, Coronavirus
- spike protein, SARS-CoV-2
- Peptidyl-Dipeptidase A
- ACE2 protein, human
- Ace2 protein, mouse
- Angiotensin-Converting Enzyme 2
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Topics |
- Angiotensin-Converting Enzyme 2
- Animals
- Betacoronavirus
(drug effects, genetics, isolation & purification, ultrastructure)
- Blood Vessels
(virology)
- COVID-19
- Chlorocebus aethiops
- Coronavirus Infections
(drug therapy)
- Humans
- Kidney
(cytology, virology)
- Mice
- Organoids
(virology)
- Pandemics
- Peptidyl-Dipeptidase A
(genetics, metabolism, pharmacology)
- Pneumonia, Viral
(drug therapy)
- Receptors, Virus
(metabolism)
- Recombinant Proteins
(pharmacology)
- SARS-CoV-2
- Spike Glycoprotein, Coronavirus
(metabolism)
- Vero Cells
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