5,6-二基黄通过阻止病毒进入宿主细胞来发挥抗贝塔冠状病毒活性
Yujia Cao1, Kah Man Lai2, Hongling Zheng1
1Department of Food Science and Technology, National University of Singapore, Singapore 117542, Singapore.
Virus research
|April 25, 2025
概括
5,6-二基黄 (5,6-DHF) 对SARS-CoV-2 Omicron EG.5.1.1和其他β冠状病毒 (β-CoV) 具有强烈的抗病毒活性. 这种化合物通过阻断尖峰-ACE2相互作用来抑制病毒的进入,表明其作为治疗候选者的潜力.
科学领域:
- 病毒学 病毒学
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
背景情况:
- 来自Scutellaria baicalensis Georgi的Baicalin通过准病毒3C类蛋白酶 (3CLpro) 来抑制SARS-CoV-2.
- 有限的数据存在于5,6-dihydroxyflavone (5,6-DHF) 的抗病毒潜力,一个baicalin类似物,对betacoronaviruses (beta-CoVs).
研究的目的:
- 为了研究5,6-DHF的抗SARS-CoV-2和抗β-CoV活性.
- 阐明5,6-DHF对SARS-CoV-2 Omicron变异EG.5.1.1.1.的作用机制.
主要方法:
- 微中和化试验 (MNT) 和斑块减少中和化试验 (PRNT) 用于评估抗病毒活性.
- 使用3CLpro抑制试验,添加时间试验,分子对接和伪型病毒进入试验来确定作用机制.
- 通过在5,6-DHF上修改基组来探索结构-活性关系.
主要成果:
- 5,6-DHF对SARS-CoV-2 Omicron变种EG.5.1.1的活性比baicalein.1.1更强.
- 在5,6-DHF的A环上的5,6-二氧 (甲基醇) 组对其抗病毒功效至关重要.
- 5,6-DHF通过干扰尖端蛋白的受体结合域 (RBD) 与ACE2.2的相互作用来抑制SARS-CoV-2的进入.
- 5,6-DHF还有效地抑制了人类β型冠状病毒OC43 (HCoV-OC43) 的进入.
结论:
- 5,6-DHF是SARS-CoV-2 Omicron变异EG.5.1.1和HCoV-OC43入口的强有力的抑制剂.
- 该化合物的机制涉及阻断尖峰-ACE2相互作用.
- 5,6-DHF显示为对抗各种β-CoVs的治疗候选物具有前途.
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