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Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids

COVID-19-associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and modulation of the renin-angiotensin II signaling (RAS) pathway by viral infection remain poorly charac...

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Autores principales: Rahmani, Waleed, Chung, Hyunjae, Sinha, Sarthak, Bui-Marinos, Maxwell P., Arora, Rohit, Jaffer, Arzina, Corcoran, Jennifer A., Biernaskie, Jeff, Chun, Justin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795780/
https://www.ncbi.nlm.nih.gov/pubmed/35106453
http://dx.doi.org/10.1016/j.isci.2022.103818
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author Rahmani, Waleed
Chung, Hyunjae
Sinha, Sarthak
Bui-Marinos, Maxwell P.
Arora, Rohit
Jaffer, Arzina
Corcoran, Jennifer A.
Biernaskie, Jeff
Chun, Justin
author_facet Rahmani, Waleed
Chung, Hyunjae
Sinha, Sarthak
Bui-Marinos, Maxwell P.
Arora, Rohit
Jaffer, Arzina
Corcoran, Jennifer A.
Biernaskie, Jeff
Chun, Justin
author_sort Rahmani, Waleed
collection PubMed
description COVID-19-associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and modulation of the renin-angiotensin II signaling (RAS) pathway by viral infection remain poorly characterized. Using induced pluripotent stem cell-derived kidney organoids, SARS-CoV-1, SARS-CoV-2, and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2, NRP1 or DPP4) and protease (TMPRSS2, TMPRSS4, FURIN, CTSB or CTSL), was identified primarily among proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in patients with COVID-19, inhibited angiotensin II-mediated internalization of ACE2, upregulated interferon-stimulated genes (IFITM1 and BST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection.
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spelling pubmed-87957802022-01-28 Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids Rahmani, Waleed Chung, Hyunjae Sinha, Sarthak Bui-Marinos, Maxwell P. Arora, Rohit Jaffer, Arzina Corcoran, Jennifer A. Biernaskie, Jeff Chun, Justin iScience Article COVID-19-associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and modulation of the renin-angiotensin II signaling (RAS) pathway by viral infection remain poorly characterized. Using induced pluripotent stem cell-derived kidney organoids, SARS-CoV-1, SARS-CoV-2, and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2, NRP1 or DPP4) and protease (TMPRSS2, TMPRSS4, FURIN, CTSB or CTSL), was identified primarily among proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in patients with COVID-19, inhibited angiotensin II-mediated internalization of ACE2, upregulated interferon-stimulated genes (IFITM1 and BST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection. Elsevier 2022-01-28 /pmc/articles/PMC8795780/ /pubmed/35106453 http://dx.doi.org/10.1016/j.isci.2022.103818 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Rahmani, Waleed
Chung, Hyunjae
Sinha, Sarthak
Bui-Marinos, Maxwell P.
Arora, Rohit
Jaffer, Arzina
Corcoran, Jennifer A.
Biernaskie, Jeff
Chun, Justin
Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids
title Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids
title_full Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids
title_fullStr Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids
title_full_unstemmed Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids
title_short Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids
title_sort attenuation of sars-cov-2 infection by losartan in human kidney organoids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795780/
https://www.ncbi.nlm.nih.gov/pubmed/35106453
http://dx.doi.org/10.1016/j.isci.2022.103818
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