ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-OR04

A Novel Soluble ACE2 Protein Protects from Lethal SARS-CoV-2 Infection

Session Information

Category: Coronavirus (COVID-19)

  • 000 Coronavirus (COVID-19)

Authors

  • Hassler, Luise, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Gelarden, Ian A., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Tomatsidou, Anastasia, The University of Chicago, Chicago, Illinois, United States
  • Gula, Haley, The University of Chicago, Chicago, Illinois, United States
  • Nicolaescu, Vlad I., The University of Chicago, Chicago, Illinois, United States
  • Randall, Glenn, The University of Chicago, Chicago, Illinois, United States
  • Yeldandi, Anjana, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) uses full-length angiotensin converting enzyme 2 (ACE2) as the main receptor to enter the target cells. A novel soluble ACE2 protein with increased duration of action and binding capacity to exert a decoy effect as a way to intercept SARS-CoV-2 from binding to membrane-bound ACE2 was generated. The protein was administered to a lethal mouse model of COVID-19 to examine its efficacy.

Methods

A human soluble ACE2 variant fused with a 5kD albumin binding domain (ABD) was linked via a dimerization motif hinge-like 4-cysteine dodecapeptide to improve binding capacity to the SARS-CoV-2. This novel protein (ACE2 1-618-DDC-ABD) was administered intranasally and intraperitoneally prior to viral inoculation and on the two following consecutive days. Infected animals were observed for weight, clinical score and mortality in a BSL-3 facility. Upon sacrifice, lung histopathology was evaluated, and viral loads were measured by plaque assay.

Results

Infected mice that received ACE2-1-618-DDC-ABD developed only moderate disease assessed by a clinical score, modest weight loss and lung histology. At 6 days, mortality was totally prevented in the treated group (figure), lung histopathology was markedly improved and viral lung and brain titers reduced or non-detectable. By contrast, in untreated animals, lung histology revealed extensive pulmonary alveolar hemorrhage and mononuclear infiltrates, and they all became severely ill and had to be euthanized by day 6/7 (figure).

Conclusion

This study demonstrates for the first time in vivo the preventative/ therapeutic efficacy of a soluble ACE2 protein in a preclinical animal model.

Funding

  • Private Foundation Support