Inhibition of SARS-CoV-2 infections in engineered human tissues by soluble ACE2.
In a recent publication in Cell, Swedish virologist Ali Mirazimi and coauthors, report on the blockade of SARS-CoV-2 infection by human, recombinant, soluble angiotensin converting enzyme 2 (hrsACE2). Inhibition of virus replication was demonstrated in single cell kidney cell cultures as well as in organoids of blood vessel and kidney origins. These results provide promising and important knowledge for the development of antiviral drugs targeting SARS-CoV-2 infection.
Vanessa Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, Hurtado del Pozo C, Prosper F, Romero JP, Wirnsberger G, Zhang H, Slutsky AS, Conder R, Montserrat N*, Mirazimi A*, Penninger JM*. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. DOI: 10.1016/j.cell.2020.04.004
We have previously provided the first genetic evidence that Angiotensin converting enzyme 2 (ACE2) is the critical receptor for SARS-CoV and that 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.