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

Cell. 2020 May 14;181(4):905-913.e7. doi: 10.1016/j.cell.2020.04.004. Epub 2020 Apr 24.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Betacoronavirus / drug effects*
  • Betacoronavirus / genetics
  • Betacoronavirus / isolation & purification
  • Betacoronavirus / ultrastructure
  • Blood Vessels / virology
  • Chlorocebus aethiops
  • Coronavirus Infections / drug therapy*
  • Humans
  • Kidney / cytology
  • Kidney / virology
  • Mice
  • Organoids / virology
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Peptidyl-Dipeptidase A / pharmacology*
  • Pneumonia, Viral / drug therapy*
  • Receptors, Virus / metabolism
  • Recombinant Proteins / pharmacology*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vero Cells

Substances

  • Receptors, Virus
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2