期刊
SCIENCE ADVANCES
卷 7, 期 22, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abh0319
关键词
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资金
- NIH [1R35GM137905-01]
- CTSI pilot grant
- University of Pittsburgh
- Center for Vaccine Research
- Commonwealth of Pennsylvania Department of Community and Economic Development
- Richard King Mellon Foundation
- Henry L. Hillman Foundation
The study demonstrates the high efficacy of PiN-21 in preventing and treating SARS-CoV-2 infection in Syrian hamsters modeling moderate to severe COVID-19. Intranasal delivery of PiN-21 effectively protects infected animals from weight loss and reduces viral burdens in both lower and upper airways.
Globally, there is an urgency to develop effective, low-cost therapeutic interventions for coronavirus disease 2019 (COVID-19). We previously generated the stable and ultrapotent homotrimeric Pittsburgh inhalable Nanobody 21 (PiN-21). Using Syrian hamsters that model moderate to severe COVID-19 disease, we demonstrate the high efficacy of PiN-21 to prevent and treat SARS-CoV-2 infection. Intranasal delivery of PiN-21 at 0.6 mg/kg protects infected animals from weight loss and substantially reduces viral burdens in both lower and upper airways compared to control. Aerosol delivery of PiN-21 facilitates deposition throughout the respiratory tract and dose minimization to 0.2 mg/kg. Inhalation treatment quickly reverses animals' weight loss after infection, decreases lung viral titers by 6 logs leading to drastically mitigated lung pathology, and prevents viral pneumonia. Combined with the marked stability and low production cost, this innovative therapy may provide a convenient and cost-effective option to mitigate the ongoing pandemic.
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