Cianfarini, C.; Hassler, L.; Wysocki, J.; Hassan, A.; Nicolaescu, V.; Elli, D.; Gula, H.; Ibrahim, A.M.; Randall, G.; Henkin, J.; Batlle, D. 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. Cells2024, 13, 203.
Cianfarini, C.; Hassler, L.; Wysocki, J.; Hassan, A.; Nicolaescu, V.; Elli, D.; Gula, H.; Ibrahim, A.M.; Randall, G.; Henkin, J.; Batlle, D. 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. Cells 2024, 13, 203.
Cianfarini, C.; Hassler, L.; Wysocki, J.; Hassan, A.; Nicolaescu, V.; Elli, D.; Gula, H.; Ibrahim, A.M.; Randall, G.; Henkin, J.; Batlle, D. 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. Cells2024, 13, 203.
Cianfarini, C.; Hassler, L.; Wysocki, J.; Hassan, A.; Nicolaescu, V.; Elli, D.; Gula, H.; Ibrahim, A.M.; Randall, G.; Henkin, J.; Batlle, D. 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. Cells 2024, 13, 203.
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 have 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 (2x104 PFU) and followed for up to 14 days. ACE2-618-DDC-ABD (10mg/kg) or PBS was administered intranasally six hours prior and 24 and 48 hours post viral inoculation. All animals in the PBS-control group had succumbed to the disease on day 7 post infection (0% survival) whereas, by 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 by 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 extended duration of action in protecting against the aggressive delta SARS-CoV-2 variant. Together with previous work these findings demonstrate the universal protective potential against current and future emerging SARS-CoV-2 variants.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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