SARS-CoV-2 感染取决于细胞肝酸盐和ACE2
Thomas Mandel Clausen1, Daniel R Sandoval2, Charlotte B Spliid1
1Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark.
SARS-CoV-2 尖端蛋白使用细胞肝素硫酸盐来增强与 ACE2 的结合,从而促进病毒感染. 肝素和相关分子可以阻止这种相互作用,提供新的治疗策略.
科学领域:
- 病毒学
- 生物化学
- 分子生物学
背景情况:
- 严重急性呼吸综合征冠状病毒2 (SARS-CoV-2) 使用其尖端蛋白进入细胞.
- 血管酶转化酶2 (ACE2) 是SARS-CoV-2的主要宿主细胞受体.
研究的目的:
- 调查肝酸盐 (HS) 在SARS-CoV-2尖端蛋白与ACE2结合中的作用.
- 探索针对治疗干预的HS-spike蛋白相互作用的潜力.
主要方法:
- 在体外结合测试中使用纯化的尖端蛋白,ACE2和肝素.
- 在接研究中预测结合点.
- 用伪型和真实SARS-CoV-2病毒进行基于细胞的测试.
- 电子显微镜可视化尖端蛋白质的结构.
主要成果:
- SARS-CoV-2 尖端蛋白的受体结合域 (RBD) 与 HS 和 ACE2 相互作用.
- HS和ACE2独立地与尖端蛋白结合,HS作为支架形成三元复合体.
- 肝素增强了RBD的开放形状,促进了ACE2结合.
- 结合尖端蛋白和病毒感染的细胞依赖于HS和ACE2.
- 各种形式的肝素和HS有效地阻断了尖端蛋白的结合和病毒感染.
结论:
- 肝酸盐通过增强与ACE2结合的尖端蛋白质,在SARS-CoV-2的附着和感染中起着至关重要的作用.
- 针对肝素硫酸与尖端蛋白的相互作用,为抗击SARS-CoV-2提供了一个有前途的治疗策略.
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