tetano
Editor, Senior Moderator
Cells
. 2024 Jan 23;13(3):203.
doi: 10.3390/cells13030203. 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[SUP] 1 2 [/SUP], Luise Hassler[SUP] 1 [/SUP], Jan Wysocki[SUP] 1 [/SUP], Abdelsabour Hassan[SUP] 1 [/SUP], Vlad Nicolaescu[SUP] 3 [/SUP], Derek Elli[SUP] 3 [/SUP], Haley Gula[SUP] 3 [/SUP], Amany M Ibrahim[SUP] 3 [/SUP], Glenn Randall[SUP] 3 [/SUP], Jack Henkin[SUP] 4 [/SUP], Daniel Batlle[SUP] 1 [/SUP]
Affiliations
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 × 10[SUP]4[/SUP] 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.
Keywords: ACE2; COVID-19; SARS-CoV-2; angiotensin-converting enzyme 2.
. 2024 Jan 23;13(3):203.
doi: 10.3390/cells13030203. 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[SUP] 1 2 [/SUP], Luise Hassler[SUP] 1 [/SUP], Jan Wysocki[SUP] 1 [/SUP], Abdelsabour Hassan[SUP] 1 [/SUP], Vlad Nicolaescu[SUP] 3 [/SUP], Derek Elli[SUP] 3 [/SUP], Haley Gula[SUP] 3 [/SUP], Amany M Ibrahim[SUP] 3 [/SUP], Glenn Randall[SUP] 3 [/SUP], Jack Henkin[SUP] 4 [/SUP], Daniel Batlle[SUP] 1 [/SUP]
Affiliations
- PMID: 38334597
- PMCID: PMC10854654
- DOI: 10.3390/cells13030203
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 × 10[SUP]4[/SUP] 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.
Keywords: ACE2; COVID-19; SARS-CoV-2; angiotensin-converting enzyme 2.