Intranasal soluble ACE2 improves survival and prevents brain SARS-CoV-2 infection.
Life Sci Alliance
; 6(7)2023 07.
Article
in English
| MEDLINE | ID: covidwho-2296268
ABSTRACT
A soluble ACE2 protein bioengineered for long duration of action and high affinity to SARS-CoV-2 was administered either intranasally (IN) or intraperitoneally (IP) to SARS-CoV-2-inoculated k18hACE2 mice. This decoy protein (ACE2 618-DDC-ABD) was given either IN or IP, pre- and post-inoculation, or IN, IP, or IN + IP but only post-inoculation. Survival by day 5 was 0% in untreated mice, 40% in the IP-pre, and 90% in the IN-pre group. In the IN-pre group, brain histopathology was essentially normal and lung histopathology significantly improved. Consistent with this, brain SARS-CoV-2 titers were undetectable and lung titers reduced in the IN-pre group. When ACE2 618-DDC-ABD was administered only post-inoculation, survival was 30% in the IN + IP, 20% in the IN, and 20% in the IP group. We conclude that ACE2 618-DDC-ABD results in markedly improved survival and provides organ protection when given intranasally as compared with when given either systemically or after viral inoculation, and that lowering brain titers is a critical determinant of survival and organ protection.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Angiotensin-Converting Enzyme 2
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
Language:
English
Year:
2023
Document Type:
Article
Affiliation country:
Lsa.202301969
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