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      SARS-CoV-2 infection of kidney organoids prevented with soluble human ACE2

      Nature Reviews. Nephrology

      Nature Publishing Group UK

      SARS-CoV-2, Nephrology

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          Abstract

          The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus gains entry to host cells via ACE2, which is expressed by type 2 alveolar epithelial cells in the lungs and by cells in other tissues, including the heart, kidney and blood vessels. Researchers now show that SARS-CoV-2 can infect human blood vessel and kidney organoids and that this infection can be inhibited by human recombinant soluble ACE2 (hrsACE2). To assess whether hrsACE2 — a decoy protein that has already been tested in phase I and II clinical trials — can inhibit the interaction between SARS-CoV-2 and ACE2, Josef Penninger, Ali Mirazimi, Nuria Montserrat and colleagues administered the recombinant protein to SARS-CoV-2-infected Vero E6 cells. Treatment of cells with hrsACE2 inhibited SARS-CoV-2 infection in a dose-dependent manner and attenuated propagation of the virus. Based on the hypothesis that the presence of ACE2 in extrapulmonary tissues might explain the multi-organ dysfunction caused by COVID-19, the researchers developed human capillary organoids from induced pluripotent stem cells, and kidney organoids from human embryonic stem cells. “Importantly, single-cell RNA sequencing of the kidney organoids showed that ACE2 is expressed in different cell populations, including tubular-like cells and podocyte-like cells,” says Montserrat. Following infection of the organoids with SARS-CoV-2 the researchers could detect viral RNA that increased in the days following infection, indicative of viral replication. Addition of hrsACE2, however, again reduced SARS-CoV-2 levels in a dose-dependent manner. “Our findings not only suggest that tissue organoids can be used to study the effects of SARS-CoV-2 on extrapulmonary tissues, but also suggest that rhsACE2 might block the virus from entering target cells,” says Penninger.

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          Author and article information

          Contributors
          nrneph@nature.com
          Journal
          Nat Rev Nephrol
          Nat Rev Nephrol
          Nature Reviews. Nephrology
          Nature Publishing Group UK (London )
          1759-5061
          1759-507X
          24 April 2020
          : 1
          Affiliations
          Nature Reviews Nephrology, http://www.nature.com/nrneph
          Article
          291
          10.1038/s41581-020-0291-8
          7187150
          © Springer Nature Limited 2020

          This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

          Categories
          Research Highlight

          nephrology, sars-cov-2

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