Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses

Nambulli, S.; Xiang, Y.; Tilston-Lunel, N. L.; Rennick, L. J.; Sang, Z.; Klimstra, W. B.; Reed, D. S.; Crossland, N. A.; Shi, Y.; Duprex, P. W.

doi:10.1101/2021.02.23.432569

bioRxiv · 10.1101/2021.02.23.432569

Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses

Nambulli, S.·Xiang, Y.·Tilston-Lunel, N. L.·Rennick, L. J.·Sang, Z.·Klimstra, W. B.·Reed, D. S.·Crossland, N. A.·Shi, Y.·Duprex, P. W.

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Abstract

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.

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Nambulli, S., Xiang, Y., Tilston-Lunel, N. L., Rennick, L. J., Sang, Z., Klimstra, W. B., Reed, D. S., Crossland, N. A., Shi, Y., Duprex, P. W.. 2021-02-23. Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses. https://doi.org/10.1101/2021.02.23.432569

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