Intranasal soluble ACE2 improves survival and prevents brain SARS-CoV-2 infection.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
03
02
2023
revised:
01
04
2023
accepted:
04
04
2023
medline:
13
4
2023
entrez:
11
4
2023
pubmed:
12
4
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37041017
pii: 6/7/e202301969
doi: 10.26508/lsa.202301969
pmc: PMC10098141
pii:
doi:
Substances chimiques
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL153122
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG049665
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL154998
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI166940
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149883
Pays : United States
Informations de copyright
© 2023 Hassler et al.
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