素通过向3CLpropro对猪肠道冠状病毒表现出广泛的抗病毒活性
Xiaoxu Xing1, Jiongze Cheng1, Huinan Li1
1College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Sartu District, Daqing 163319, China.
Veterinary microbiology
|February 6, 2026
概括
丁作为猪肠道冠状病毒 (SECoVs) 的广泛抗病毒药物表现有前途. 这种天然化合物有效地抑制病毒复制,并保护小猪免受猪流行性腹病毒 (PEDV) 的感染,提供了一种新的治疗途径.
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
- 分子生物学分子生物学
背景情况:
- 猪肠道冠状病毒 (SECoVs),包括PEDV,TGEV和PDCoV,在全球猪生产中造成重大经济损失.
- 目前对SECoV的控制策略是不理想的,混合感染需要开发新的抗病毒药物.
研究的目的:
- 调查黄素作为对SECoVs的广泛抗病毒剂的潜力.
- 阐明黄素的作用机制,特别是与3C类蛋白酶 (3CLpro) 的相互作用.
主要方法:
- 使用分子对接和动力学模拟来评估氨酸与PEDV 3CLpro.pro.的结合亲和力.
- 分子层干涉测量证实了直接结合和量化亲和力.
- 在体外测定测量了3CLpro酶抑制和病毒复制抑制.
- 一个小猪模型被用来评估黄素在体内对PEDV挑战的疗效.
- 在体外测试也进行了TGEV和PDCoV.
主要成果:
- 氨酸显示稳定,高亲和度的结合PEDV 3CLpro (KD = 236 nM).
- 素显著抑制了PEDV 3CLpro活性 (IC50 = 18.74 μM),并抑制了病毒复制.
- 在小猪中,黄素提供了75%的保护,减少了临床症状,减轻了肠道损伤,降低了病毒载量.
- 素还显示了高亲和度的结合TGEV和PDCoV3CLpro,以及体外广泛的抗病毒活性 (TGEV的EC50=13.14μM,PDCoV=4.10μM).
结论:
- 丁是一种强大的PEDV抑制剂,对其他SECoVs表现出广泛的抗病毒活性.
- 氨酸的机制涉及准3CLpro酶.
- 这些发现支持黄素作为控制猪中SECoV感染的有希望的治疗候选物.
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