TY - JOUR T1 - Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses JF - bioRxiv DO - 10.1101/2021.02.23.432569 SP - 2021.02.23.432569 AU - Sham Nambulli AU - Yufei Xiang AU - Natasha L. Tilston-Lunel AU - Linda J. Rennick AU - Zhe Sang AU - William B. Klimstra AU - Douglas S. Reed AU - Nicholas A. Crossland AU - Yi Shi AU - W. Paul Duprex Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/02/23/2021.02.23.432569.abstract N2 - 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 post-infection and 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 novel therapy may provide a convenient and cost-effective option to mitigate the ongoing pandemic.Competing Interest StatementThe authors have declared no competing interest. ER -