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

Vanessa Monteil | Zendy; Hyesoo Kwon | Zendy; Patricia Prado | Zendy; Astrid Hagelkrüys | Zendy; Reiner Wimmer | Zendy; Martin Ståhl | Zendy; Alexandra Leopoldi | Zendy; Elena Garreta | Zendy; Carmen Hurtado del Pozo | Zendy; Felipe Prósper | Zendy; Juan P. Romero | Zendy; Gerald Wirnsberger | Zendy; Haibo Zhang | Zendy; Arthur S. Slutsky | Zendy; Ryan Conder | Zendy; Núria Montserrat | Zendy; Alì Mirazimi | Zendy; Josef Penninger | Zendy

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

Author(s) -

Vanessa Monteil,

Hyesoo Kwon,

Patricia Prado,

Astrid Hagelkrüys,

Reiner Wimmer,

Martin Ståhl,

Alexandra Leopoldi,

Elena Garreta,

Carmen Hurtado del Pozo,

Felipe Prósper,

Juan P. Romero,

Gerald Wirnsberger,

Haibo Zhang,

Arthur S. Slutsky,

Ryan Conder,

Núria Montserrat,

Alì Mirazimi,

Josef Penninger

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.04.004

Subject(s) - biology , vero cell , covid-19 , virology , angiotensin converting enzyme 2 , coronavirus , recombinant dna , receptor , lung , organoid , betacoronavirus , hek 293 cells , virus , immunology , gene , microbiology and biotechnology , medicine , genetics , disease , outbreak , infectious disease (medical specialty)

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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