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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Apr 26

PMID 32333836

Citations 1316

Authors

Vanessa Monteil

Hyesoo Kwon

Patricia Prado

Astrid Hagelkruys

Reiner A Wimmer

Martin Stahl

Alexandra Leopoldi

Elena Garreta

Carmen Hurtado Del Pozo

Felipe Prosper

Juan Pablo Romero

Gerald Wirnsberger

Haibo Zhang

Arthur S Slutsky

Ryan Conder

Nuria Montserrat

Ali Mirazimi

Josef M Penninger

Affiliations

Soon will be listed here.

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.

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