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通过仿制甘氨酸的聚合物对抗DC-SIGN介导的SARS-CoV-2传播
Jonathan Cramer1,2, Xiaohua Jiang1, Butrint Aliu1
1Department of Pharmaceutical Sciences, Group Molecular Pharmacy, Pharmazentrum, University of Basel, Basel, Switzerland.
Archiv der Pharmazie
|December 12, 2023
概括
针对树突细胞特异性ICAM-3抓取非整体素 (DC-SIGN) 的新型甘氨酸衍生配体在抑制病毒进入方面表现出高强度. 这些多价DC-SIGN配体为广谱抗病毒疗法提供了一个有前途的战略.
科学领域:
- 病毒学 病毒学
- 碳水化合物化学 碳水化合物化学
- 免疫学 免疫学 免疫学
背景情况:
- 许多病毒利用树突细胞特异性的ICAM-3抓取非整体素 (DC-SIGN) 进入细胞并传播.
- 通过糖甘配体抑制DC-SIGN介导的病毒附着是一种潜在的宽谱抗病毒策略.
研究的目的:
- 评估多价DC-SIGN联体,由寡甘和复杂类型甘氨酸衍生,用于抗病毒应用.
- 在单价和多价水平上研究联体受体相互作用的热力学.
主要方法:
- 在聚-l-氨酸支架上合成具有特定碳水化合物表位体 (oligomannosides,α-l-Fuc) 的多价格甘油聚合物.
- 对配体与四价DC-SIGN受体进行热力学结合研究.
- 细胞测试以评估病毒附着和DC-SIGN介导传播的抑制.
主要成果:
- 甘油聚合物在抑制DC-SIGN介导病毒附着 (pico-到nanomolar范围) 中表现出高强度.
- 橄曼诺斯表位体表现出显著的活动.
- 多价联体在细胞模型中显示有效抑制病毒传播.
结论:
- 多价DC-SIGN配体,特别是那些具有寡曼诺斯表位体的多价DC-SIGN配体,是病毒进入和传播的强效抑制剂.
- 生物相容的poly-l-lysine支架支持这些糖聚合物的进一步临床前开发,作为广泛的抗病毒药物.
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