ACE2 CAN INHIBIT SARS-CoV-2 infections.

Volume 181, Issue 4, 14 May 2020, Pages 905-913.e7

Article

Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2

Author links open overlay panelVanessaMonteil1HyesooKwon2PatriciaPrado3AstridHagelkrüys4Reiner A.Wimmer4MartinStahl5AlexandraLeopoldi4ElenaGarreta3CarmenHurtado del Pozo3FelipeProsper6Juan PabloRomero6GeraldWirnsberger7HaiboZhang8Arthur S.Slutsky8RyanConder5NuriaMontserrat3910AliMirazimi12Josef M.Penninger41112

https://doi.org/10.1016/j.cell.2020.04.004Get rights and content

open access

Highlights

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Soluble human ACE2 can inhibit SARS-CoV-2 infections

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SARS-CoV-2 can directly infect human blood vessel and kidney organoids

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Human organoids as model systems to study SARS-CoV-2 infections/COVID-19

Summary

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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