Vanessa Monteil 1 , Hyesoo Kwon 2 , Patricia Prado 3 , Astrid Hagelkrüys 4 , Reiner A. Wimmer 4 , Martin Stahl 5 , Alexandra Leopoldi 4 , Elena Garreta 3 , Carmen Hurtado del Pozo 3 , Felipe Prosper 6 , Juan Pablo Romero 6 , Gerald Wirnsberger 7 , Haibo Zhang 8 , Arthur S. Slutsky 8 , Ryan Conder 5 , Nuria Montserrat 3 , 9 , 10 , ∗ , Ali Mirazimi 1 , 2 , ∗∗ , Josef M. Penninger 4 , 11 , 12 , ∗∗∗
24 April 2020
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.
Clinical-grade recombinant human ACE2 can reduce SARS-CoV-2 infection in cells and in multiple human organoid models.