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一个基于马类iPSC的表型查平台识别了对西尼罗河病毒的亲和抗病毒分子

Marielle Cochet¹, François Piumi¹, Kamila Gorna¹

¹UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.

Veterinary research

|March 17, 2024

概括

一种新的马类脑细胞模型有效地选了西尼罗河病毒 (WNV) 的抗病毒化合物. 2'C-methylcytidine显示出有希望的结果,而他类药物意外地恶化了马匹的WNV感染.

科学领域:

兽医病毒学兽医病毒学
药物发现药物发现药物发现
干细胞生物学干细胞生物学

背景情况:

西尼罗河病毒 (WNV) 爆发影响人类和马匹的健康,疫苗有效性有限,马匹没有特定的抗病毒治疗方法.
目前的药物发现模型经常使用动物或灵长类动物的细胞,限制了结果的可转化到马类生理学.
对于特定于马类的细胞模型来准确评估抗病毒疗法是非常需要的.

研究的目的:

为WNV感染研究开发一种新的体外马类脑细胞模型.
在马类环境中选化学化合物库以检测WNV的抗病毒活性.
识别潜在的治疗线索,了解特定物种的药物反应.

主要方法:

使用诱导多能干细胞生成一种马类脑细胞模型.
在马脑细胞中建立西尼罗病毒 (WNV) 感染的体外模型.
对41种化学化合物的细胞毒性和抗病毒功效进行基于微板检测的选.

主要成果:

核类比的2'C-甲基丁证明了在马类脑细胞中显著抑制了WNV感染.
在人类细胞系中有效的几个化合物在马类模型中是有毒的或无效的.
类药物在WNV感染的马类脑细胞中表现出意想不到的前病毒效应.

结论:

开发的马脑细胞模型是评估抗病毒化合物对西尼罗河病毒 (WNV) 的相关平台.
2'C-甲基丁代表了一种潜在的化合物,用于马类WNV的治疗发展.
特定于物种和组织的细胞模型对于准确的临床前抗病毒药物评估至关重要.

关键词:

马类动物马类动物弗拉维病毒 (flavivirus) 是一种病毒.这是一种抗病毒药物.大脑大脑大脑的大脑大脑神经原始体的神经祖先核酸类比的核酸类比斯塔丁是一个国家.

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