tetano
Editor, Senior Moderator
Cell. 2020 Apr 17. pii: S0092-8674(20)30399-8. doi: 10.1016/j.cell.2020.04.004. [Epub ahead of print]
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.
Monteil V[SUP]1[/SUP], Kwon H[SUP]2[/SUP], Prado P[SUP]3[/SUP], Hagelkr?ys A[SUP]4[/SUP], Wimmer RA[SUP]4[/SUP], Stahl M[SUP]5[/SUP], Leopoldi A[SUP]4[/SUP], Garreta E[SUP]3[/SUP], Hurtado Del Pozo C[SUP]3[/SUP], Prosper F[SUP]6[/SUP], Romero JP[SUP]6[/SUP], Wirnsberger G[SUP]7[/SUP], Zhang H[SUP]8[/SUP], Slutsky AS[SUP]8[/SUP], Conder R[SUP]5[/SUP], Montserrat N[SUP]9[/SUP], Mirazimi A[SUP]10[/SUP], Penninger JM[SUP]11[/SUP].
Author information
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.
Copyright ? 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
COVID-19; angiotensin converting enzyme 2; blood vessels; human organoids; kidney; severe acute respiratory syndrome coronavirus; spike glycoproteins; treatment
PMID:32333836DOI:10.1016/j.cell.2020.04.004
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.
Monteil V[SUP]1[/SUP], Kwon H[SUP]2[/SUP], Prado P[SUP]3[/SUP], Hagelkr?ys A[SUP]4[/SUP], Wimmer RA[SUP]4[/SUP], Stahl M[SUP]5[/SUP], Leopoldi A[SUP]4[/SUP], Garreta E[SUP]3[/SUP], Hurtado Del Pozo C[SUP]3[/SUP], Prosper F[SUP]6[/SUP], Romero JP[SUP]6[/SUP], Wirnsberger G[SUP]7[/SUP], Zhang H[SUP]8[/SUP], Slutsky AS[SUP]8[/SUP], Conder R[SUP]5[/SUP], Montserrat N[SUP]9[/SUP], Mirazimi A[SUP]10[/SUP], Penninger JM[SUP]11[/SUP].
Author information
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.
Copyright ? 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
COVID-19; angiotensin converting enzyme 2; blood vessels; human organoids; kidney; severe acute respiratory syndrome coronavirus; spike glycoproteins; treatment
PMID:32333836DOI:10.1016/j.cell.2020.04.004