Nambulli, ShamXiang, YufeiTilston-Lunel, Natasha L.Rennick, Linda J.Sang, ZheKlimstra, William B.Reed, Douglas S.Crossland, Nicholas A.Shi, YiDuprex, W. Paul2025-04-042025-04-042021-05-26Nambulli S, Xiang Y, Tilston-Lunel NL, et al. Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses. Sci Adv. 2021;7(22):eabh0319. Published 2021 May 26. doi:10.1126/sciadv.abh0319https://hdl.handle.net/1805/46840Globally, 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.en-USAttribution-NonCommercial 4.0 InternationalCOVID-19AerosolsMesocricetusSARS-CoV-2Viral pneumoniaArticle