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
Affiliations
Cosimo Cianfarini
Division of Nephrology/Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, 710 North Fairbanks Court, Chicago, IL 60611, USA
Luise Hassler
Division of Nephrology/Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, 710 North Fairbanks Court, Chicago, IL 60611, USA
Jan Wysocki
Division of Nephrology/Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, 710 North Fairbanks Court, Chicago, IL 60611, USA
Abdelsabour Hassan
Division of Nephrology/Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, 710 North Fairbanks Court, Chicago, IL 60611, USA
Vlad Nicolaescu
Howard Taylor Ricketts Laboratory, Department of Microbiology, The University of Chicago, Lemont, IL 60637, USA
Derek Elli
Howard Taylor Ricketts Laboratory, Department of Microbiology, The University of Chicago, Lemont, IL 60637, USA
Haley Gula
Howard Taylor Ricketts Laboratory, Department of Microbiology, The University of Chicago, Lemont, IL 60637, USA
Amany M. Ibrahim
Howard Taylor Ricketts Laboratory, Department of Microbiology, The University of Chicago, Lemont, IL 60637, USA
Glenn Randall
Howard Taylor Ricketts Laboratory, Department of Microbiology, The University of Chicago, Lemont, IL 60637, USA
Jack Henkin
Center for Developmental Therapeutics, Northwestern University, Evanston, IL 60208, USA
Daniel Batlle
Division of Nephrology/Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, 710 North Fairbanks Court, Chicago, IL 60611, USA
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.
