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

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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 V¹, Kwon H², Prado P³, Hagelkr?ys A⁴, Wimmer RA⁴, Stahl M⁵, Leopoldi A⁴, Garreta E³, Hurtado Del Pozo C³, Prosper F⁶, Romero JP⁶, Wirnsberger G⁷, Zhang H⁸, Slutsky AS⁸, Conder R⁵, Montserrat N⁹, Mirazimi A¹⁰, Penninger JM¹¹.

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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