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

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.

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Affiliated Institutions

• Swedish Veterinary Agency SE
• St. Michael's Hospital CA
• Karolinska University Hospital SE
• Austrian Academy of Sciences AT
• Institució Catalana de Recerca i Estudis Avançats ES
• Universidad de Navarra ES
• Vienna Biocenter AT
• University of Toronto CA
• Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine ES
• Apeiron Biologics (Austria) AT
• Institute for Bioengineering of Catalonia ES
• University of British Columbia CA
• Institute of Molecular Biotechnology AT
• Stemcell Technologies CA
• Karolinska Institutet SE

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