人类冠状病毒HKU1通过基甘受体仿真中和
Ziqi Feng1, Nurgun Kose2, Fernando R Moreira3
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
一种新的人类单克隆抗体HKU1-2通过模仿酸结合来中和人类冠状病毒HKU1 (HCoV-HKU1). 这种抗体通过准尖端蛋白的糖体受体相互作用部位来阻止病毒的进入.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 人类季节性冠状病毒HKU1 (HCoV-HKU1) 的进入依赖于酸糖和TMPRSS2.2.
- 阻止这些相互作用的抗体的中和潜力仍然未被探索.
研究的目的:
- 为了分离和描述针对HCoV-HKU1.1的人类单克隆抗体 (mAb).
- 为了研究抗体中和HCoV-HKU1感染的机制.
主要方法:
- 单克隆抗体HKU1-2的分离和表征.
- 皮层图谱绘制和结构分析,包括冷电子显微镜 (cryo-EM).
- 对抗体中和能力和受体结合模拟的评估.
主要成果:
- 分离了单克隆抗体HKU1-2,并证明了HCoV-HKU1.1的剂量依赖性中和.
- HKU1-2 准了 N 末端域的 sialoglycan 结合部位在尖端蛋白上.
- 克里奥-EM揭示HKU1-2模仿酸结合,阻止病毒进入.
- 抗体结合涉及CDRH3识别关键残留物 (K80,W89),这对于酸参与至关重要.
结论:
- 抗体HKU1-2通过模仿酸结合,有效地中和HCoV-HKU1.
- 这种受体模拟机制代表了阻止冠状病毒进入的新策略.
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