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硫酸化聚糖抑制 MERS-CoV 受体结合域与肝素的相互作用。

Sulfated Glycans Inhibit the Interaction of MERS-CoV Receptor Binding Domain with Heparin.

机构信息

The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.

Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.

出版信息

Viruses. 2024 Feb 2;16(2):237. doi: 10.3390/v16020237.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising target to inhibit viral infection. In the current study, the interaction between the receptor-binding domain (RBD) of MERS-CoV and heparin was exploited to assess the inhibitory activity of various sulfated glycans such as glycosaminoglycans, marine-sourced glycans (sulfated fucans, fucosylated chondroitin sulfates, fucoidans, and rhamnan sulfate), pentosan polysulfate, and mucopolysaccharide using Surface Plasmon Resonance. We believe this study provides valuable insights for the development of sulfated glycan-based inhibitors as potential antiviral agents.

摘要

中东呼吸综合征冠状病毒(MERS-CoV)是一种高传染性和高死亡率的人畜共患病病毒。硫酸乙酰肝素蛋白聚糖(HSPGs)广泛表达于哺乳动物细胞表面。由于其高负电荷特性,宿主细胞表面的肝素硫酸盐(HS)被许多病毒用作辅助因子,以促进病毒附着并启动细胞进入。因此,抑制病毒与 HS 之间的相互作用可能是抑制病毒感染的有前途的靶点。在本研究中,利用 MERS-CoV 的受体结合域(RBD)与肝素之间的相互作用,利用表面等离子体共振评估了各种硫酸化糖,如糖胺聚糖、海洋来源的糖(硫酸岩藻糖、硫酸软骨素、褐藻糖胶和鼠李半乳糖醛酸聚糖硫酸盐)、戊聚糖多硫酸盐和粘多糖的抑制活性。我们相信这项研究为基于硫酸化糖的抑制剂作为潜在的抗病毒药物的开发提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5212/10892611/40705817f588/viruses-16-00237-g001.jpg

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