Cell
Volume 181, Issue 4, 14 May 2020, Pages 905-913.e7
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Article
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2

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

Highlights

  • Soluble human ACE2 can inhibit SARS-CoV-2 infections

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

  • 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.

Keywords

human organoids
COVID-19
angiotensin converting enzyme 2
severe acute respiratory syndrome coronavirus
spike glycoproteins
kidney
blood vessels
treatment

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