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

tetano

Editor, Senior Moderator
Sci Adv


. 2021 May 26;7(22):eabh0319.
doi: 10.1126/sciadv.abh0319. Print 2021 May.
Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses


Sham Nambulli[SUP] 1 2 [/SUP], Yufei Xiang[SUP] 3 [/SUP], Natasha L Tilston-Lunel[SUP] 1 2 [/SUP], Linda J Rennick[SUP] 1 2 [/SUP], Zhe Sang[SUP] 3 4 [/SUP], William B Klimstra[SUP] 1 2 5 [/SUP], Douglas S Reed[SUP] 1 5 [/SUP], Nicholas A Crossland[SUP] 6 7 [/SUP], Yi Shi[SUP] 8 4 [/SUP], W Paul Duprex[SUP] 9 2 [/SUP]



Affiliations

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 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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