Author: Monteil, Vanessa; Kwon, Hyesoo; Prado, Patricia; Hagelkrüys, Astrid; Wimmer, Reiner A.; Stahl, Martin; Leopoldi, Alexandra; Garreta, Elena; Hurtado del Pozo, Carmen; Prosper, Felipe; Romero, Juan Pablo; Wirnsberger, Gerald; Zhang, Haibo; Slutsky, Arthur S.; Conder, Ryan; Montserrat, Nuria; Mirazimi, Ali; Penninger, Josef M.
Title: Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 Cord-id: 6fbftzk0 Document date: 2020_4_24
ID: 6fbftzk0
Snippet: Summary 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 pat
Document: Summary 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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