Resveratrol inhibits respiratory syncytial virus replication by targeting heparan sulfate proteoglycans
Resveratrol inhibits respiratory syncytial virus replication by targeting heparan sulfate proteoglycans
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DOI：
10.1039/d3fo05131e
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发表时间：
2024-01-11
期刊：
影响因子：
6.1
通讯作者：
Ji，Jianjian
中科院分区：
文献类型：
--
作者：
Xiong，Yingcai;Tao，Keyu;Ji，Jianjian
白藜芦醇，作为一种著名的抗氧化剂，在对抗严重呼吸道感染，特别是呼吸道合胞病毒（RSV）方面也显示出巨大的潜力。然而，其抑制RSV复制的具体机制尚不清楚。硫酸肝素蛋白聚糖（HSPGs）作为许多病毒的附着因子发挥着关键作用，为对抗病毒感染提供了一条有希望的途径。我们的研究表明，白藜芦醇以剂量依赖的方式有效地抑制RSV感染。值得注意的是，白藜芦醇通过与HSPGs结合而不是与RSV表面蛋白如融合蛋白(F)和糖蛋白(G)相互作用来破坏RSV感染的早期阶段。白藜芦醇的亲和力似乎主要针对hspg上的负电荷位点，从而阻碍病毒受体的结合。在一项涉及rsv感染小鼠的体内研究中，白藜芦醇通过改善肺部病理证明了其潜力。这种改善归因于促炎细胞因子表达的抑制和肺内病毒载量的减少。值得注意的是，白藜芦醇特异性地减轻了rsv感染小鼠中以大量中性粒细胞为特征的炎症。总之，我们的数据首先显示了白藜芦醇如何通过与hspg相互作用来对抗RSV感染，将其定位为针对RSV感染的创新药物开发的有希望的候选者。我们的研究为白藜芦醇抗病毒感染的机制提供了新的思路。
Resveratrol, renowned as an antioxidant, also exhibits significant potential in combatting severe respiratory infections, particularly the respiratory syncytial virus (RSV). Nevertheless, the specific mechanism underlying its inhibition of RSV replication remains unexplored. Heparan sulfate proteoglycans (HSPGs) play a pivotal role as attachment factors for numerous viruses, offering a promising avenue for countering viral infections. Our research has unveiled that resveratrol effectively curbs RSV infection in a dose-dependent manner. Remarkably, resveratrol disrupts the early stages of RSV infection by engaging with HSPGs, rather than interacting with RSV surface proteins like fusion (F) protein and glycoprotein (G). Resveratrol's affinity appears to be predominantly directed towards the negatively charged sites on HSPGs, thus impeding the binding of viral receptors. In an in vivo study involving RSV-infected mice, resveratrol demonstrates its potential by ameliorating pulmonary pathology. This improvement is attributed to the inhibition of pro-inflammatory cytokine expression and a reduction in viral load within the lungs. Notably, resveratrol specifically alleviates inflammation characterized by an abundance of neutrophils in RSV-infected mice. In summation, our data first shows how resveratrol combats RSV infection through interactions with HSPGs, positioning it as a promising candidate for innovative drug development targeting RSV infections. Our study provides insight into the mechanism of resveratrol antiviral infection.