Yang Jiyuan, Datta Payel, Xia Ke, Pomin Vitor H, Wang Chunyu, Qiao Mingqiang, Linhardt Robert J, Dordick Jonathan S, Zhang Fuming
The Key Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai University, Tianjin, 300071, P.R. China.
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
Glycoconj J. 2024 Dec;41(6):371-380. doi: 10.1007/s10719-024-10172-9. Epub 2024 Dec 16.
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 = 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.
登革病毒（DENV）通过蚊虫叮咬传播给人类，全球感染人数达数百万。DENV通过将包膜蛋白与靶细胞上高度硫酸化的硫酸乙酰肝素（HS）结合，利用硫酸乙酰肝素进行附着和进入细胞。因此，抑制DENV与HS之间的结合可能是预防DENV感染的一种有前景的策略。在本研究中，使用竞争溶液SPR分析了登革病毒包膜蛋白（来自2型DENV）与肝素（HS的替代物）之间的相互作用。结果表明，肝素以高亲和力（K = 8.83 nM）与登革病毒包膜蛋白结合。使用表面固定的肝素和一系列天然来源及半合成硫酸化聚糖进行的竞争溶液SPR分析表明，对登革病毒包膜蛋白与肝素的结合具有显著抑制活性。这项分子相互作用研究可为登革病毒感染治疗药物的开发提供见解。
