针对SARS-CoV-2尖端剪切器的演变,旨在优化硫酸肝素的交叉链接和链际流动性
Jurij Froese1, Marco Mandalari2,3, Monica Civera3
1Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Waldeyerstrasse 15, D-48149, Münster, Germany.
Scientific reports
|December 31, 2024
概括
SARS-CoV-2 Omicron 变种通过交叉连接肝素硫酸盐链来增强通过细胞外基质的运动. 这一发现提供了一种新的策略,可以使用酸模仿剂阻止Omicron感染.
科学领域:
- 病毒学 病毒学
- 生物化学 生化学
- 细胞外矩阵生物学 细胞外矩阵生物学
背景情况:
- 在进入细胞之前,SARS-CoV-2尖峰 (S) 蛋白最初与细胞外基质 (ECM) 中的肝素硫酸盐 (HS) 结合,然后与ACE2受体结合.
- 欧米克朗变异体现出增强的HS结合,原因是S蛋白三元体上的正电荷残留物.
- 在Omicron变种中增加的HS结合,引发了关于它们在HS丰富的ECM中的移动性的问题.
研究的目的:
- 研究SARS-CoV-2 Omicron变种中与HS相关的病毒运动背后的机制.
- 了解Omicron S蛋白质如何在增强的HS相互作用的情况下实现移动性.
- 确定潜在的治疗点来抑制Omicron变种感染.
主要方法:
- 利用HS功能化的人工矩阵研究Omicron S蛋白的移动性.
- 分析了Omicron S蛋白与HS链的交叉链接能力.
- 测试了heparan硫酸仿真剂在抑制Omicron变种结合和感染方面的疗效.
主要成果:
- 奥米克朗S蛋白在HS功能化的基质上表现出增强的移动性.
- 欧米克朗S蛋白可以交叉连接至少两个HS链,使S蛋白切换和细胞表面移动性成为可能.
- 一种特定的HS模仿剂显著抑制了Omicron变体的表面结合和细胞感染.
结论:
- 奥米克朗S蛋白已经演变为平衡HS相互作用稳定性和动态,以实现高效的运动.
- 由Omicron S-蛋白质交叉连接HS链对于它们的移动性和传染性至关重要.
- 肝酸硫酸模仿剂代表了针对SARS-CoV-2 Omicron和潜在的未来变种的有前途的治疗策略.
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