Department of Chemistry, Virginia Commonwealth University, Richmond, VA, 23284, USA.
Department of BioMolecular Sciences, University of Mississippi, University, MS, 38677, USA.
Sci Rep. 2023 Mar 23;13(1):4804. doi: 10.1038/s41598-023-31722-5.
Great interest exists towards the discovery and development of broad-spectrum antivirals. This occurs due to the frequent emergence of new viruses which can also eventually lead to pandemics. A reasonable and efficient strategy to develop new broad-spectrum antivirals relies on targeting a common molecular player of various viruses. Heparan sulfate is a sulfated glycosaminoglycan present on the surface of cells which plays a key role as co-receptor in many virus infections. In previous work, marine sulfated glycans (MSGs) were identified as having antiviral activities. Their mechanism of action relies primarily on competitive inhibition of virion binding to heparan sulfate, preventing virus attachment to the cell surface prior to entry. In the current work we used pseudotyped lentivirus particles to investigate in a comparative fashion the inhibitory properties of five structurally defined MSGs against SARS-CoV-1, SARS-CoV-2, MERS-CoV, and influenza A virus (IAV). MSGs include the disaccharide-repeating sulfated galactan from the red alga Botryocladia occidentalis, the tetrasaccharide-repeating sulfated fucans from the sea urchin Lytechinus variegatus and from the sea cucumber Isostichopus badionotus, and the two marine fucosylated chondroitin sulfates from the sea cucumbers I. badionotus and Pentacta pygmaea. Results indicate specificity of action against SARS-CoV-1 and SARS-CoV-2. Curiously, the MSGs showed decreased inhibitory potencies against MERS-CoV and negligible action against IAV. Among the five MSGs, the two sulfated fucans here studied deserve further attention since they have the lowest anticoagulant effects but still present potent and selective antiviral properties.
人们对广谱抗病毒药物的发现和开发非常感兴趣。这是因为新病毒的频繁出现也可能最终导致大流行。开发新的广谱抗病毒药物的合理且有效的策略依赖于针对各种病毒的共同分子靶点。硫酸乙酰肝素是一种存在于细胞表面的硫酸化糖胺聚糖，在许多病毒感染中作为辅助受体发挥关键作用。在以前的工作中，已经确定海洋硫酸化糖胺聚糖 (MSG) 具有抗病毒活性。其作用机制主要依赖于竞争性抑制病毒粒子与硫酸乙酰肝素的结合，从而在病毒进入细胞表面之前阻止其附着。在当前的工作中，我们使用假型慢病毒颗粒以比较的方式研究了五种结构定义明确的 MSG 对 SARS-CoV-1、SARS-CoV-2、MERS-CoV 和甲型流感病毒 (IAV) 的抑制特性。MSG 包括来自红藻 Botryocladia occidentalis 的二糖重复硫酸半乳聚糖、来自海胆 Lytechinus variegatus 和海参 Isostichopus badionotus 的四糖重复硫酸岩藻聚糖，以及来自海参 I. badionotus 和 Pentacta pygmaea 的两种海洋岩藻糖基硫酸软骨素。结果表明它们对 SARS-CoV-1 和 SARS-CoV-2 的作用具有特异性。奇怪的是，MSG 对 MERS-CoV 的抑制效力降低，对 IAV 的作用可以忽略不计。在这 5 种 MSG 中，我们研究的两种硫酸岩藻聚糖值得进一步关注，因为它们的抗凝作用最低，但仍具有强大且选择性的抗病毒特性。
