对冠状病毒HKU5 HKU5的物种特异性ACE2识别的分子洞察力
Yuanyuan Zhang1,2,3,4, Yuya Li2,3,4, Weijie Gao2,3,4
1College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Nature communications
|December 4, 2025
概括
蝙蝠冠状病毒HKU5使用其尖蛋白来结合各种物种的ACE2受体,包括鸟类. 这一发现揭示了对病毒宿主适应和动物感染潜力的洞察力,强调了监测的必要性.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 动物传播疾病 动物传播疾病
背景情况:
- 冠状病毒构成重大动物感染威胁,宿主适应是跨物种传播的关键.
- 蝙蝠冠状病毒HKU5使用其尖 (S) 蛋白进入宿主细胞.
研究的目的:
- 确定HKU5 S蛋白及其受体结合域 (RBD) 的结构.
- 调查HKU5与血管激素转化酶2 (ACE2) 的结合机制及其对动物传播的潜力.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定HKU5 S蛋白及其RBD-ACE2复合物的结构.
- 进化和功能分析,包括伪病毒入口和细胞-细胞融合试验.
主要成果:
- 冷-EM结构显示脂肪酸稳定了HKU5 S蛋白质的封闭形状.
- 在HKU5 RBD和Pipistrellus abramus ACE2之间发现了一种独特的结合模式.
- HKU5证明了结合和利用来自鸟类物种的ACE2基因组的能力,例如Pitta sordida.
结论:
- HKU5在各种物种中表现出广泛的ACE2结合和利用,这表明有显著的动物感染潜力.
- RBD中的突变可以影响受体结合,影响宿主适应.
- 持续监测HKU5是至关重要的,因为其已被证明是动物感染的风险.
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