针对SARS-CoV-2中保存表位的IgM类纳米体的增强效能增加了N-终端域的峰值
Bo Liu1,2, Honghui Liu2, Pu Han2
1College of Veterinary Medicine, Shanxi Agricultural University, 030801, Jinzhong, China.
Signal transduction and targeted therapy
|May 13, 2024
概括
一种新的纳米体,N235,通过向尖端蛋白质上的保存表位,中和SARS-CoV-2变体.
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:
- 针对SARS-CoV-2尖端蛋白的受体结合域 (RBD) 的中和抗体通常对新出现的变体失去有效性.
- 高度保存的表位对开发针对SARS-CoV-2的广泛有效的中和抗体至关重要.
研究的目的:
- 识别和描述具有广泛中和活性的纳米体,以对抗SARS-CoV-2变种.
- 阐明中和机制,并探索治疗潜力.
主要方法:
- 低温电子显微镜测定纳米体的结合部位.
- 流细胞计和西斑分析中和机制.
- 用伪型和真实病毒进行体外测定.
- 在动物模型中使用鼻内注射的体内研究.
主要成果:
- 一种纳米体,N235,对SARS-CoV-2原型和变种,包括Omicron子变种,进行了广泛的中和.
- N235在尖端蛋白的N端域 (NTD) 中结合了一种新的,保存的表位,干扰RBD.
- N235诱导S1亚单元从尖端蛋白质复合体中脱落;一个纳米-IgM结构 (MN235) 增强中和和病毒粒子交叉链接.
- 鼻内MN235在体内有效地预防了Omicron BA.1和XBB感染.
结论:
- N235针对NTD中保存的,神秘的表位,提供针对SARS-CoV-2变种的广泛中和.
- 改造的纳米-IgM (MN235) 显示出增强的疗效和潜力,作为一种预防药物,对抗当前和未来的SARS-CoV-2感染.
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