Novel mono- and multivalent N-acetylneuraminic acid glycoclusters as potential broad-spectrum entry inhibitors for influenza and coronavirus infection
作者:Xingxing Zhu、Yanliang Yi、Zibo Fan、Ruiwen Liu、Xindang Chu、Mengyang Wang、Jiayi Zhang、Elena Tretyakova、Yongmin Zhang、Lihe Zhang、Demin Zhou、Sulong Xiao
DOI:10.1016/j.ejmech.2023.115723
日期:2023.11
N-acetylneuraminic acid (Neu5Ac) is a glycan receptor of viruses spread in many eukaryotic cells. The present work aimed to design, synthesis and biological evaluation of a panel of Neu5Ac derivatives based on a cyclodextrin (CD) scaffold for targeting influenza and coronavirus membrane proteins. The multivalent Neu5Ac glycoclusters efficiently inhibited chicken erythrocyte agglutination induced by
N-乙酰神经氨酸 (Neu5Ac) 是在许多真核细胞中传播的病毒的聚糖受体。目前的工作旨在设计、合成和生物学评估一组基于环糊精 (CD) 支架的 Neu5Ac 衍生物,用于靶向流感和冠状病毒膜蛋白。多价 Neu5Ac 糖簇以 Neu5Ac 密度依赖性方式有效抑制完整流感病毒诱导的鸡红细胞凝集。与Neu5Ac的抑制相比, β -CD支架主面上具有21个Neu5Ac残基的多价抑制剂对流感病毒血凝素的结合亲和力抑制高1788倍,解离常数(K D)为3.87 × 10 -7 M它对流感病毒神经氨酸酶表现出中等的结合亲和力,但其效力仅为 HA 蛋白的约三十分之一。它还对三种人类冠状病毒(严重急性呼吸综合征冠状病毒、中东呼吸综合征冠状病毒和严重急性呼吸综合征冠状病毒2)的刺突蛋白表现出很强的结合亲和力,KD值在低微摩尔范围内,约为10 -时间比HA弱。因此,这些多价唾液酸化 CD 衍生物通过靶向宿主细胞的