天然产品Sennoside B通过抑制其RNA结合活性来破坏SARS-CoV-2核体蛋白质的液-液相分离
Da-Wei Zhang1, Xiao-Shuang Xu1, Liangxu Xie1
1Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, China.
Journal of enzyme inhibition and medicinal chemistry
|May 15, 2025
概括
鉴定出两种天然产品 - - 赛诺西德A和B - - 作为SARS-CoV-2核蛋白 (NP) - - RNA相互作用和液体液相分离 (LLPS) 的抑制剂,为新的抗病毒药物开发提供了潜力.
科学领域:
- 病毒学 病毒学
- 生物化学 生化学
- 药物发现 药物发现 药物发现
背景情况:
- SARS-CoV-2核蛋白 (NP) 是一种RNA结合蛋白,对于病毒复制和组装至关重要.
- NP经历液-液相分离 (LLPS),这是病毒生命周期和免疫逃避至关重要的过程.
研究的目的:
- 开发一种高通量查方法,用于识别SARS-CoV-2 NP-RNA相互作用的抑制剂.
- 发现可以破坏NP-RNA结合和NP LLPS的新型化合物.
主要方法:
- 对NP-RNA相互作用抑制的均质时间解析光 (HTRF) 试验.
- 生物层干涉测量以确认直接的NP结合.
- 在光漂白后的光恢复 (FRAP) 来评估NP LLPS的抑制.
主要成果:
- 鉴定出赛诺酸A和赛诺酸B是SARS-CoV-2 NP-RNA相互作用的抑制剂.
- 两种 sennosides 都直接与 NP 结合,结合点位于 C 终端域.
- 赛诺B有效抑制了RNA诱导的NPLLPS,而赛诺A显示出较弱的活性.
结论:
- HTRF测试是发现SARS-CoV-2 NP-RNA结合和LLPS.抑制剂的宝贵工具.
- 赛诺化物A和B显示出作为开发针对NP功能的新型SARS-CoV-2抗病毒疗法的化合物的潜力.
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