Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin.

IF 2.7 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Glycoconjugate Journal Pub Date : 2024-12-16 DOI:10.1007/s10719-024-10172-9

Jiyuan Yang, Payel Datta, Ke Xia, Vitor H Pomin, Chunyu Wang, Mingqiang Qiao, Robert J Linhardt, Jonathan S Dordick, Fuming Zhang

引用次数: 0

Abstract

Dengue viruses (DENV) are transmitted to humans through mosquito bites and infect millions globally. DENV uses heparan sulfate (HS) for attachment and cell entry by binding the envelope protein to highly sulfated HS on target cells. Therefore, inhibiting the binding between DENV and HS could be a promising strategy for preventing DENV infection. In the current study, the interactions between DENV envelope protein (from Type 2 DENV) and heparin (a surrogate for HS) were analyzed using competition solution SPR. Results demonstrate that heparin binds to DENV envelope protein with high affinity (K_D = 8.83 nM). Competitive Solution SPR assays using surface-immobilized heparin and a series of naturally-sourced and semi-synthetic sulfated glycans demonstrated significant inhibitory activity against the binding of DENV envelope proteins to heparin. This study of molecular interactions could provide insights into the development of therapeutics for DENV infection.

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登革热病毒（DENV）通过蚊子叮咬传播给人类，全球有数百万人受到感染。DENV 通过将包膜蛋白与靶细胞上高度硫酸化的硫酸纤维素结合，利用硫酸肝素（HS）附着和进入细胞。因此，抑制 DENV 与 HS 之间的结合可能是预防 DENV 感染的一种有效策略。本研究利用竞争溶液 SPR 分析了 DENV 包膜蛋白（来自 2 型 DENV）和肝素（HS 的替代物）之间的相互作用。结果表明，肝素与 DENV 包膜蛋白的结合亲和力很高（KD = 8.83 nM）。使用表面固定的肝素和一系列天然来源的半合成硫酸化聚糖进行的竞争溶液 SPR 分析表明，肝素对 DENV 包膜蛋白与肝素的结合具有显著的抑制活性。这项分子相互作用研究可为开发治疗 DENV 感染的药物提供启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Glycoconjugate Journal 生物-生化与分子生物学

CiteScore

6.00

自引率

3.30%

发文量

审稿时长

1 months

期刊介绍： Glycoconjugate Journal publishes articles and reviews on all areas concerned with: function, composition, structure, biosynthesis, degradation, interactions, recognition and chemo-enzymatic synthesis of glycoconjugates (glycoproteins, glycolipids, oligosaccharides, polysaccharides and proteoglycans), biochemistry, molecular biology, biotechnology, immunology and cell biology of glycoconjugates, aspects related to disease processes (immunological, inflammatory, arthritic infections, metabolic disorders, malignancy, neurological disorders), structural and functional glycomics, glycoimmunology, glycovaccines, organic synthesis of glycoconjugates and the development of methodologies if biologically relevant, glycosylation changes in disease if focused on either the discovery of a novel disease marker or the improved understanding of some basic pathological mechanism, articles on the effects of toxicological agents (alcohol, tobacco, narcotics, environmental agents) on glycosylation, and the use of glycotherapeutics. Glycoconjugate Journal is the official journal of the International Glycoconjugate Organization, which is responsible for organizing the biennial International Symposia on Glycoconjugates.