鉴定新的福衍生物作为具有广谱抗病毒活性的STING激动剂
A Paulis1, A Onali1, P O Vidalain2
1Department of Life and Environmental Sciences, University of Cagliari, Monserrato 09042, Italy.
Virus research
|July 5, 2024
概括
新的福衍生物作为干扰素基因刺激剂 (STING) 激动剂,增强抗病毒免疫力. 这些化合物在抑制冠状病毒复制方面表现有前途,为广泛的抗病毒药物开发提供了一个新的支架.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 药用化学 医学化学
背景情况:
- 干扰素基因刺激器 (STING) 途径对先天免疫至关重要,它调解细胞质DNA传感和I型干扰素 (IFN-I) 诱导.
- 佐和津衍生物以其生物活性而闻名,这表明药物发现中可能存在相关的支架.
研究的目的:
- 通过使用松衍生物,识别具有抗病毒性能的新型STING激动剂.
- 评估这些化合物诱导IFN-I和抑制病毒复制,特别是冠状病毒的能力.
主要方法:
- 化合物被选使用 luciferase 记者测定IFN-β促进体活性在STING表达细胞.
- 使用具有突变STING的细胞证实了结合特异性.
- 对接研究预测了绑定模式.
- 在各种细胞系中对人类冠状病毒229E和SARS-CoV-2进行了抗病毒活性评估.
- 通过分析-IRF3局部化和IFN缺乏细胞中的测试,证实了IFN依赖活性.
主要成果:
- 七种松衍生物以STING-依赖的方式诱导IFN-β转录.
- 三种化合物显示出对HCoV-229E的微米范围内的EC50值的抗冠状病毒活性.
- 这些衍生物在纳米分子度下抑制了SARS-CoV-2的复制.
- 证实活性依赖于IFN,因为化合物在缺乏IFN生产的Vero E6细胞中是不活跃的.
结论:
- 福衍生物被确定为依赖STING的免疫刺激化合物.
- 这些化合物作为冠状病毒的宿主向抑制剂.
- 酸是一种新的化学支架,用于开发广泛的抗病毒药物.
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