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

      Nature Reviews Nephrology

      Springer Science and Business Media LLC

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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

          Journal
          Nature Reviews Nephrology
          Nat Rev Nephrol
          Springer Science and Business Media LLC
          1759-5061
          1759-507X
          April 24 2020
          Article
          10.1038/s41581-020-0291-8
          © 2020

          Free to read

          http://www.springer.com/tdm

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