Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters.
Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters.
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DOI：
10.3390/v15081744
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发表时间：
2023-08-15
期刊：
影响因子：
--
通讯作者：
Owen A
中科院分区：
文献类型：
--
作者：
Neary M;Sharp J;Gallardo-Toledo E;Herriott J;Kijak E;Bramwell C;Cox H;Tatham L;Box H;Curley P;Arshad U;Rajoli RKR;Pertinez H;Valentijn A;Dhaliwal K;Mc Caughan F;Hobson J;Rannard S;Kipar A;Stewart JP;Owen A
针对SARS-CoV-2的化学预防的成功开发可以提供一种可与疫苗接种方案一起实施的感染预防工具。那法莫斯特是一种丝氨酸蛋白酶抑制剂，在体外可以抑制SARS-CoV-2的进入，但它尚未被用于动物模型的化学预防。临床上，奈法莫斯特仅限于静脉给药，且血浆半衰期极短。本研究旨在确定鼻腔给药5 mg/kg，每天两次，是否能够阻止SARS-CoV-2通过空气传播给未感染的叙利亚金黄地鼠。与接种SARS-CoV-2的金黄地鼠同居4d后，水处理对照组的咽拭子中检测到SARS-CoV-2RNA。然而，鼻腔内用那法莫司治疗的仓鼠的咽拭子在整整4天的同居过程中仍然是SARS-CoV-2RNA阴性。治疗组鼻甲中SARS-CoV-2RNA浓度显著低于对照组(p=0.001)。空斑分析结果显示，与对照组相比，服用那法莫司特的患者肺内传染性非典型肺炎冠状病毒-2的浓度显著降低(p=0.035)。综合肺部和鼻黏膜的病理变化来看，这些数据有力地支持了鼻腔给药在预防SARS-CoV-2感染方面的效用。
The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (p = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (p = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection.
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影响因子：
6.4
作者：
Li K;Meyerholz DK;Bartlett JA;McCray PB Jr
通讯作者：
McCray PB Jr
DOI：
10.1016/j.ijid.2020.10.093
发表时间：
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期刊：
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
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作者：
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DOI：
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发表时间：
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期刊：
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通讯作者：
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影响因子：
64.8
作者：
Meng B;Abdullahi A;Ferreira IATM;Goonawardane N;Saito A;Kimura I;Yamasoba D;Gerber PP;Fatihi S;Rathore S;Zepeda SK;Papa G;Kemp SA;Ikeda T;Toyoda M;Tan TS;Kuramochi J;Mitsunaga S;Ueno T;Shirakawa K;Takaori-Kondo A;Brevini T;Mallery DL;Charles OJ;CITIID-NIHR BioResource COVID-19 Collaboration;Genotype to Phenotype Japan (G2P-Japan) Consortium;Ecuador-COVID19 Consortium;Bowen JE;Joshi A;Walls AC;Jackson L;Martin D;Smith KGC;Bradley J;Briggs JAG;Choi J;Madissoon E;Meyer KB;Mlcochova P;Ceron-Gutierrez L;Doffinger R;Teichmann SA;Fisher AJ;Pizzuto MS;de Marco A;Corti D;Hosmillo M;Lee JH;James LC;Thukral L;Veesler D;Sigal A;Sampaziotis F;Goodfellow IG;Matheson NJ;Sato K;Gupta RK
通讯作者：
Gupta RK
DOI：
10.1016/j.cvex.2011.03.007
发表时间：
2011-05-01
期刊：
Veterinary Clinics of North America Exotic Animal Practice
影响因子：
--
作者：
Kling, Melissa A.
通讯作者：
Kling, Melissa A.