主体肝硫酸盐促进了ACE2超级集群的组装,并增强了SARS-CoV-2相关的同位素形成
Qi Zhang1,2, Weichun Tang3, Eduardo Stancanelli4
1Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Nature communications
|September 18, 2023
概括
细胞表面肝硫酸盐 (HS) 对于SARS-CoV-2尖端蛋白来说至关重要,可以诱导细胞融合,形成与严重COVID相关的合成细胞. 用药物准HS可能会减少突细胞和病毒感染.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 感染SARS-CoV-2导致合成细胞的形成,导致严重的COVID-19.
- 尖蛋白调解细胞与ACE2表达细胞的细胞融合.
研究的目的:
- 为了阐明尖端诱导的同胞体形成的机制.
- 为了确定参与SARS-CoV-2介导细胞融合的宿主因素.
主要方法:
- 化学遗传学和4D共聚焦成像被使用.
- 研究了细胞表面硫酸肝素 (HS) 在尖端诱导的融合中的作用.
- 使用纯化的ACE2和尖端的无细胞系统.
主要成果:
- 肝硫酸盐 (HS) 被确定为尖端诱导的细胞融合的关键刺激剂.
- HS与尖蛋白结合,促进ACE2聚类和突触形成.
- 抑制HS减少了同胞体的形成;HS直接刺激了在无细胞系统中的ACE2聚类.
- 在HS刺激的融合中,需要一个与尖端结合部位不同的ACE2链接区域.
结论:
- 肝硫酸盐 (HS) 是SARS-CoV-2用于受体聚类和同位素形成的关键宿主因子.
- 用一种研究药物向HS减少了体外同胞细胞的形成和小鼠的病毒感染.
- HS代表了严重的COVID-19的潜在治疗目标.
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