人类小气道表皮揭示了二乙作为对呼吸道病毒的广泛抗病毒药物
Paula Martínez de Iturrate1, Bruno Hernáez2, Patricia de Los Santos1
1Centro de Investigaciones Biológicas Margarita Salas, CSIC, 28040 Madrid, Spain.
二乙酸盐 (DCA) 是一种广谱抗病毒药物. 这项研究发现,在先进的人类细胞模型中,DCA对呼吸道病毒有效,这突显了查模型对药物发现的重要性.
科学领域:
- 病毒学 病毒学
- 细胞的新陈代谢
- 药物发现 药物发现 药物发现
背景情况:
- 呼吸道病毒感染对全球健康构成重大风险.
- 随着COVID-19的爆发,人们越来越需要广泛的抗病毒药物和更好的临床前模型.
- 病毒经常重新编程宿主细胞代谢以促进复制.
研究的目的:
- 研究PI3K/AKT/mTOR通路抑制剂对呼吸道病毒的疗效.
- 将不同细胞模型中的抗病毒活性进行比较,重点关注代谢适应.
- 评估二乙酸盐 (DCA) 作为一种潜在的针对宿主细胞代谢的抗病毒药物.
主要方法:
- 在MRC5肺纤维细胞和Huh7肝瘤细胞中对PI3K/AKT/mTOR途径抑制剂的比较分析.
- 评估HCoV-229E感染后的代谢概况和抗病毒活性.
- 在人类小气道上皮细胞的3D空气-液体接口模型中对二乙酸盐 (DCA) 的测试.
主要成果:
- 二乙酸盐 (DCA) 在MRC5细胞中表现出对HCoV-229E的抗病毒活性,但不是Huh7细胞.
- 临床前查模型的选择显著影响了观察到的抗病毒效应.
- 在3D人体呼吸系统模型中,DCA使HCoV-229E,SARS-CoV-2和RSV的病毒后代减少了2-3个数量级,即使在感染后给药时也是如此.
结论:
- 临床前查模型对于识别有效的针对宿主代谢途径的抗病毒药物至关重要.
- 二乙 (DCA) 是一种可行的概念验证候选人,用于针对呼吸道病毒的广泛抗病毒疗法.
- 针对宿主代谢途径提供了一种策略,可以对抗各种病毒感染,并可能减少耐药性.
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