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米瑞素通过向类似帕帕因的蛋白酶二基化酶活性来抑制传染性胃肠炎病毒的复制
Jiahao Fan1, Pengyuan Xi1, Huimao Liu1
1Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Frontiers in microbiology
|July 25, 2024
概括
瑞是一种天然化合物,通过抑制其蛋白酶,有效地对抗传染性胃肠炎病毒 (TGEV). 这种黄胺在预防和治疗猪中TGEV感染方面表现有前途.
科学领域:
- 兽医病毒学 兽医病毒学
- 自然产品化学 自然产品化学
- 分子病毒学分子病毒学
背景情况:
- 传染性胃肠炎病毒 (TGEV) 是一种阿尔法冠状病毒,在猪业中造成了相当大的经济损失.
- 病毒类帕帕因类蛋白酶 (PLpro) 对于TGEV通过duebiquitination进行免疫逃避至关重要,使其成为抗病毒策略的关键目标.
研究的目的:
- 为了研究myricetin对TGEV的抗病毒潜力.
- 阐明myricetin抗病毒活性的机制,重点关注其与TGEV PLpro.pro的相互作用.
主要方法:
- 在体外抗病毒试验中评估myricetin对TGEV诱导的细胞病变效应和病毒载荷的影响.
- 酶抑制试验和分子对接,以确定myricetin与TGEV PLpro.pro的相互作用.
- 基于细胞的测定和局部定向的突变发生,以确认结合机制.
主要成果:
- 瑞显示TGEV的剂量依赖性抑制,EC50为31.19μM,并显著降低病毒载量.
- 瑞直接禁用TGEV并抑制其复制,对PK-15细胞表现出保护作用.
- 密瑞可以竞争性地抑制TGEV PLpro,其IC50为6.563μM,通过键和其他相互作用与Cys102残留物结合.
结论:
- 瑞对TGEV具有显著的抗病毒活性.
- 瑞作为TGEV PLpro的竞争性抑制剂,破坏病毒复制和免疫逃避.
- 米瑞是预防和治疗猪TGEV感染的有前途的治疗候选药物.
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