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

TLDR

ACE2 is the critical receptor for SARS‑CoV and SARS‑CoV‑2, protects the lung, and its inhibition has been proposed as a COVID‑19 therapy, though it was unclear whether soluble recombinant ACE2 could block viral growth. The authors demonstrated that SARS‑CoV‑2 infects engineered human blood vessel and kidney organoids, and that soluble recombinant human ACE2 (hrsACE2) can inhibit this infection. Clinical‑grade hrsACE2 reduced SARS‑CoV‑2 recovery from Vero cells by 1,000–5,000×, inhibited infection of human organoids, and thus effectively blocks early stages of SARS‑CoV‑2 infection, whereas mouse rsACE2 had no effect.

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.