Intranasal soluble ACE2 improves survival and prevents brain SARS-CoV-2 infection

Luise Hassler, Jan Wysocki, Jared T. Ahrendsen, Minghao Ye, Ian Gelarden, Vlad Nicolaescu, Anastasia Tomatsidou, Haley Gula, Cosimo Cianfarini, Peter Forster, Nigar Anjuman Khurram, Benjamin D. Singer, Glenn Randall, Dominique Missiakas, Jack Henkin, Daniel Batlle

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article numbere202301969
JournalLife science alliance
Volume6
Issue number7
DOIs
StatePublished - Jul 2023

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Health, Toxicology and Mutagenesis
  • Plant Science
  • Ecology

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