Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Mar Drugs. 2023 Apr 25;21(5):264. doi: 10.3390/md21050264.
Sulfated glycans from marine organisms are excellent sources of naturally occurring glycosaminoglycan (GAG) mimetics that demonstrate therapeutic activities, such as antiviral/microbial infection, anticoagulant, anticancer, and anti-inflammation activities. Many viruses use the heparan sulfate (HS) GAG on the surface of host cells as co-receptors for attachment and initiating cell entry. Therefore, virion-HS interactions have been targeted to develop broad-spectrum antiviral therapeutics. Here we report the potential anti-monkeypox virus (MPXV) activities of eight defined marine sulfated glycans, three fucosylated chondroitin sulfates, and three sulfated fucans extracted from the sea cucumber species , , and , and the sea urchin , as well as two chemically desulfated derivatives. The inhibitions of these marine sulfated glycans on MPXV A29 and A35 protein-heparin interactions were evaluated using surface plasmon resonance (SPR). These results demonstrated that the viral surface proteins of MPXV A29 and A35 bound to heparin, which is a highly sulfated HS, and sulfated glycans from sea cucumbers showed strong inhibition of MPXV A29 and A35 interactions. The study of molecular interactions between viral proteins and host cell GAGs is important in developing therapeutics for the prevention and treatment of MPXV.
海洋生物来源的硫酸化糖胺聚糖是天然存在的糖胺聚糖 (GAG) 类似物的极好来源，这些类似物具有治疗活性，如抗病毒/微生物感染、抗凝血、抗癌和抗炎活性。许多病毒将宿主细胞表面的肝素硫酸盐 (HS) GAG 用作附着和启动细胞进入的共受体。因此，病毒 - HS 相互作用已成为开发广谱抗病毒治疗药物的目标。在这里，我们报告了来自海参物种 、 、 和 以及海胆 的八种定义明确的海洋硫酸化糖胺聚糖、三种岩藻糖基硫酸软骨素和三种硫酸化岩藻聚糖以及两种化学去硫酸化衍生物的潜在抗猴痘病毒 (MPXV) 活性。使用表面等离子体共振 (SPR) 评估了这些海洋硫酸化糖胺聚糖对 MPXV A29 和 A35 蛋白-肝素相互作用的抑制作用。这些结果表明，MPXV A29 和 A35 的病毒表面蛋白与肝素结合，肝素是一种高度硫酸化的 HS，海参来源的硫酸化糖胺聚糖强烈抑制 MPXV A29 和 A35 的相互作用。研究病毒蛋白与宿主细胞 GAG 之间的分子相互作用对于开发预防和治疗 MPXV 的治疗方法非常重要。
