Antiviral activity of marine sulfated glycans against pathogenic human coronaviruses.

Antiviral activity of marine sulfated glycans against pathogenic human coronaviruses.
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DOI:
10.1038/s41598-023-31722-5
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发表时间:
2023-03-23
期刊:
影响因子:
4.6
通讯作者:
Pomin, Vitor H.
Pomin, Vitor H.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zoepfl, Mary;Dwivedi, Rohini;Kim, Seon Beom;McVoy, Michael A.;Pomin, Vitor H.

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人们对广谱抗病毒药物的发现和开发存在极大的兴趣。这是由于新病毒的频繁出现,最终也可能导致大流行。开发新的广谱抗病毒药物的合理和有效的策略依赖于靶向各种病毒的共同分子。硫酸乙酰肝素是存在于细胞表面的硫酸化糖胺聚糖,其在许多病毒感染中作为共受体起关键作用。在以前的工作中,海洋硫酸化聚糖(MSG)被确定为具有抗病毒活性。它们的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,防止病毒在进入细胞前附着在细胞表面。在目前的工作中,我们使用假型慢病毒颗粒,以比较的方式研究了五种结构确定的MSG对SARS-CoV-1,SARS-CoV-2,MERS-CoV和甲型流感病毒(IAV)的抑制特性。味精包括来自红葡萄藻的二硫代硫酸酯重复硫酸化半乳聚糖、来自海胆Lytechinus variegatus和海参Isostichopus badionotus的四硫代硫酸酯重复硫酸化岩藻聚糖以及来自海参I的两种海洋岩藻糖基化软骨素硫酸盐。badionotus和Pentacta pygmaea。结果表明对SARS-CoV-1和SARS-CoV-2的作用特异性。奇怪的是,MSG对MERS-CoV的抑制效力降低,对IAV的作用可忽略不计。在五种味精中,本文研究的两种硫酸化岩藻聚糖值得进一步关注,因为它们具有最低的抗凝血作用,但仍具有有效和选择性的抗病毒特性。
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.
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