Internal medicine

Receptor

Virus

Disease

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Biology

Gene

Outbreak

Virology

HEK 293 cells

Immunology

Lung

Angiotensin-converting enzyme 2

Betacoronavirus

Coronavirus

2019-20 coronavirus outbreak

Organoid

Recombinant DNA

Cell biology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Genetics

Medicine

Vero cell

Cell

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.

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