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...

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Autores: 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, Wirnberger, Gerald, Zhang, Haibo, Slutsky, Arthur S., Conder, Ryan, Montserrat, Núria, Mirazimi, Ali, Penninger, Josef M.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/165519
Acceso en línea:https://hdl.handle.net/2445/165519
Access Level:acceso abierto
Palabra clave:Coronavirus
SARS-CoV-2
Terapèutica
Coronaviruses
Therapeutics
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spelling Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2Monteil, VanessaKwon, HyesooPrado, PatriciaHagelkrüys, AstridWimmer, Reiner A.Stahl, MartinLeopoldi, AlexandraGarreta, ElenaHurtado del Pozo, CarmenProsper, FelipeRomero, Juan PabloWirnberger, GeraldZhang, HaiboSlutsky, Arthur S.Conder, RyanMontserrat, NúriaMirazimi, AliPenninger, Josef M.CoronavirusSARS-CoV-2TerapèuticaCoronavirusesSARS-CoV-2TherapeuticsWe 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.Elsevier202020212020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion9 p.application/pdfhttps://hdl.handle.net/2445/165519Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1016/j.cell.2020.04.004Cell, 2020, vol. 181, num. 4, p. 905-913https://doi.org/10.1016/j.cell.2020.04.004info:eu-repo/grantAgreement/EC/H2020/640525icc-by-nc-nd (c) Elsevier, 2020http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1655192026-05-29T05:05:01Z
dc.title.none.fl_str_mv 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
spellingShingle Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2
Monteil, Vanessa
Coronavirus
SARS-CoV-2
Terapèutica
Coronaviruses
SARS-CoV-2
Therapeutics
title_short 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_sort Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2
dc.creator.none.fl_str_mv 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
Wirnberger, Gerald
Zhang, Haibo
Slutsky, Arthur S.
Conder, Ryan
Montserrat, Núria
Mirazimi, Ali
Penninger, Josef M.
author Monteil, Vanessa
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
Wirnberger, Gerald
Zhang, Haibo
Slutsky, Arthur S.
Conder, Ryan
Montserrat, Núria
Mirazimi, Ali
Penninger, Josef M.
author_role author
author2 Kwon, Hyesoo
Prado, Patricia
Hagelkrüys, Astrid
Wimmer, Reiner A.
Stahl, Martin
Leopoldi, Alexandra
Garreta, Elena
Hurtado del Pozo, Carmen
Prosper, Felipe
Romero, Juan Pablo
Wirnberger, Gerald
Zhang, Haibo
Slutsky, Arthur S.
Conder, Ryan
Montserrat, Núria
Mirazimi, Ali
Penninger, Josef M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Coronavirus
SARS-CoV-2
Terapèutica
Coronaviruses
SARS-CoV-2
Therapeutics
topic Coronavirus
SARS-CoV-2
Terapèutica
Coronaviruses
SARS-CoV-2
Therapeutics
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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/165519
url https://hdl.handle.net/2445/165519
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.cell.2020.04.004
Cell, 2020, vol. 181, num. 4, p. 905-913
https://doi.org/10.1016/j.cell.2020.04.004
info:eu-repo/grantAgreement/EC/H2020/640525i
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier, 2020
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier, 2020
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869402702134378496
score 15.811543

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