Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses.
Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses.
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DOI：
10.1126/sciadv.abh0319
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发表时间：
2021-05
期刊：
影响因子：
13.6
通讯作者：
Duprex WP
中科院分区：
文献类型：
--
作者：
Nambulli S;Xiang Y;Tilston-Lunel NL;Rennick LJ;Sang Z;Klimstra WB;Reed DS;Crossland NA;Shi Y;Duprex WP
超高效纳米体气溶胶递送有效预防和治疗SARS-CoV-2感染。在全球范围内，迫切需要针对2019年冠状病毒病（COVID-19）开发有效、低成本的治疗干预措施。我们之前制备了稳定的超高效的同源三聚体匹兹堡可吸入纳米体21 （PiN-21）。我们利用模拟中至重度COVID-19疾病的叙利亚仓鼠，证明了PiN-21预防和治疗SARS-CoV-2感染的高效能。与对照组相比，经鼻给药0.6 mg/kg的PiN-21可保护受感染动物免受体重减轻的影响，并大大减少下呼吸道和上呼吸道的病毒负担。气溶胶递送PiN-21促进整个呼吸道的沉积和剂量最小化至0.2 mg/kg。吸入治疗可迅速逆转动物感染后的体重下降，将肺部病毒滴度降低6个对数，从而显著减轻肺部病理，并预防病毒性肺炎。结合显著的稳定性和低生产成本，这种创新疗法可能为缓解目前的大流行提供一种方便和具有成本效益的选择。
Aerosol delivery of an ultrapotent nanobody efficiently prevents and treats SARS-CoV-2 infection. 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.