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那法莫司他对人原代细支气管上皮细胞中的新型冠状病毒2（SARS-CoV-2）和季节性冠状病毒具有广泛的抗病毒和抗炎功效。

Broad antiviral and anti-inflammatory efficacy of nafamostat against SARS-CoV-2 and seasonal coronaviruses in primary human bronchiolar epithelia.

作者信息

Niemeyer Brian F, Miller Caitlin M, Ledesma-Feliciano Carmen, Morrison James H, Jimenez-Valdes Rocio, Clifton Clarissa, Poeschla Eric M, Benam Kambez H

机构信息

Division of Pulmonary Allergy and Critical Care Medicine Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA.

Division of Infectious Diseases Department of Medicine Anschutz Medical Campus University of Colorado School of Medicine Aurora Colorado USA.

出版信息

Nano Sel. 2022 Feb;3(2):437-449. doi: 10.1002/nano.202100123. Epub 2021 Jun 30.

DOI:10.1002/nano.202100123
PMID:34541574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8441815/
Abstract

Antiviral strategies that target host systems needed for SARS-CoV-2 replication and pathogenesis may have therapeutic potential and help mitigate resistance development. Here, we evaluate nafamostat mesylate, a potent broad-spectrum serine protease inhibitor that blocks host protease activation of the viral spike protein. SARS-CoV-2 is used to infect human polarized mucociliated primary bronchiolar epithelia reconstituted with cells derived from healthy donors, smokers and subjects with chronic obstructive pulmonary disease. Nafamostat markedly inhibits apical shedding of SARS-CoV-2 from all donors (log reduction). We also observe, for the first-time, anti-inflammatory effects of nafamostat on airway epithelia independent of its antiviral effects, suggesting a dual therapeutic advantage in the treatment of COVID-19. Nafamostat also exhibits antiviral properties against the seasonal human coronaviruses 229E and NL6. These findings suggest therapeutic promise for nafamostat in treating SARS-CoV-2 and other human coronaviruses.

摘要

针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）复制和发病机制所需宿主系统的抗病毒策略可能具有治疗潜力，并有助于减轻耐药性的产生。在此，我们评估甲磺酸萘莫司他，一种强效的广谱丝氨酸蛋白酶抑制剂，它可阻断病毒刺突蛋白的宿主蛋白酶激活。利用SARS-CoV-2感染由健康供体、吸烟者和慢性阻塞性肺疾病患者来源的细胞重建的人极化黏液纤毛初级细支气管上皮细胞。甲磺酸萘莫司他显著抑制来自所有供体的SARS-CoV-2的顶端脱落（对数减少）。我们还首次观察到甲磺酸萘莫司他对气道上皮细胞具有独立于其抗病毒作用的抗炎作用，这表明在治疗2019冠状病毒病（COVID-19）方面具有双重治疗优势。甲磺酸萘莫司他对季节性人类冠状病毒229E和NL6也具有抗病毒特性。这些发现表明甲磺酸萘莫司他在治疗SARS-CoV-2和其他人类冠状病毒方面具有治疗前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/639bd892c1bf/NANO-3-437-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/67442f9bc4f6/NANO-3-437-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/f5465c8ffbd2/NANO-3-437-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/57209fd2a489/NANO-3-437-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/d7f2ee0b41b6/NANO-3-437-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/639bd892c1bf/NANO-3-437-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/67442f9bc4f6/NANO-3-437-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/f5465c8ffbd2/NANO-3-437-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/57209fd2a489/NANO-3-437-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/d7f2ee0b41b6/NANO-3-437-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d19/8441815/639bd892c1bf/NANO-3-437-g004.jpg

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