Soluble Angiotensin-Converting Enzyme 2 Protein Improves Survival and Lowers Viral Titers in Lethal Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Type 2 Infection with the Delta Variant

Cosimo Cianfarini, Luise Hassler, Jan Wysocki, Abdelsabour Hassan, Vlad Nicolaescu, Derek Elli, Haley Gula, Amany M. Ibrahim, Glenn Randall, Jack Henkin, Daniel Batlle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) utilizes angiotensin-converting enzyme 2 (ACE2) as its main receptor for cell entry. We bioengineered a soluble ACE2 protein termed ACE2 618-DDC-ABD that has increased binding to SARS-CoV-2 and prolonged duration of action. Here, we investigated the protective effect of this protein when administered intranasally to k18-hACE2 mice infected with the aggressive SARS-CoV-2 Delta variant. k18-hACE2 mice were infected with the SARS-CoV-2 Delta variant by inoculation of a lethal dose (2 × 104 PFU). ACE2 618-DDC-ABD (10 mg/kg) or PBS was administered intranasally six hours prior and 24 and 48 h post-viral inoculation. All animals in the PBS control group succumbed to the disease on day seven post-infection (0% survival), whereas, in contrast, there was only one casualty in the group that received ACE2 618-DDC-ABD (90% survival). Mice in the ACE2 618-DDC-ABD group had minimal disease as assessed using a clinical score and stable weight, and both brain and lung viral titers were markedly reduced. These findings demonstrate the efficacy of a bioengineered soluble ACE2 decoy with an extended duration of action in protecting against the aggressive Delta SARS-CoV-2 variant. Together with previous work, these findings underline the universal protective potential against current and future emerging SARS-CoV-2 variants.

Original languageEnglish (US)
Article number203
JournalCells
Volume13
Issue number3
DOIs
StatePublished - Feb 2024

Keywords

  • ACE2
  • COVID-19
  • SARS-CoV-2
  • angiotensin-converting enzyme 2

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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