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

By V. Monteil, Hyesoo Kwon, Patricia Prado, Astrid Hagelkrüys, Reiner A. Wimmer, M. Stahl, Alexandra Leopoldi, E. Garreta, C. Hurtado del Pozo, F. Prósper and 8 more. Cell, 2020

1,991 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/a67094c8a919a7cef8dddcc468917a50e3ca191d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. S. Pöhlmann
2. Richard C. Becker
3. Yi Zhang
4. M. Hoffmann

Citations in the corpus

• COVID-19 update: Covid-19-associated coagulopathy (2020, background): “This hypothesis will require testing-ideally, in the form of prospectively designed substudies of ongoing clinical trials targeting SARS-CoV-2 and its associated cytotoxic and heightened inflammatory properties.”
• SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies (2021, positive): “, 2020), and these processes can be disrupted by soluble ACE2 and serine protease inhibitors (Hoffmann et al., 2020b; Monteil et al., 2020; Zhou et al., 2020).”
• SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues (2020, neutral): “For example, examining the efficacy of recombinant human ACE2 to act as a decoy receptor or the effect of ‘‘ACE inhibitors’’ in patients with, or at risk for, COVID-19 will require careful experimentation in appropriate models together with well-controlled clinical trials (Hofmann et al., 2004; Mont”
• SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19 (2020, background): “Recombinant human ACE2 protein has been reported to inhibit SARS-CoV-2 infection in engineered human tissues [60].”
• The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic (2021, positive): “Omicron spike is inhibited by soluble ACE2 but is resistant against several antibodies used for COVID-19 treatment We next asked whether the Omicron spike can be inhibited by soluble ACE2, which binds to the RBD, blocks host-cell entry, and is currently being developed for COVID-19 therapy (Monteil ”
• A Review of SARS-CoV-2 and the Ongoing Clinical Trials (2020, background): “Indeed, in a recent study, it was reported that rhACE2 could inhibit SARS-CoV-2 replication in cellular and embryonic stem cell-derived organoids by a factor 1,000-5,000 times [58].”