Pterostilbene Exhibits Broad-Spectrum Antiviral Activity by Targeting the Enterovirus Capsid, Inactivating Viral Particles, Blocking Viral Binding, and Protecting Mice From Lethal EV-A71 Challenge.

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Kuan-Ting Chuang, Siao-Cian Pan, Bor-Luen Chiang, Shih-Hsun Chen, Min-Hsiung Pan, Yu-Li Chen, Cheng-Sheng Lin, Chun-Kai Pan, Jing-Yi Lin, Yu-Li Lin
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引用次数: 0

Abstract

Human enteroviruses (EVs) are a major public health issue worldwide owing to their potential to cause respiratory illnesses, hand-foot-and-mouth disease, and severe neurological complications. Currently, no effective drugs or multivalent vaccines are available. Pterostilbene (Pte), a naturally occurring compound found in blueberries and other plants, is a type of stilbene with a similar structure to resveratrol. Pterostilbene exerts antioxidant, anti-inflammatory, and anticancer properties. However, few studies have explored its antiviral activity. This study aimed to investigate the anti-enteroviral effect and mechanisms of Pte against EV-A71 and EV-D68. Cytotoxicity and antiviral assays were performed to assess the safety of Pte to cells and its antiviral effects against enteroviruses. Viral attachment, inactivation assays, cellular receptor binding, western blotting, time-of-addition and time-of-removal assays, particle stability thermal release assay, and molecular docking were performed to elucidate the antiviral mechanisms of Pte. Additionally, we validated the antiviral effects of Pte using in vivo experiments. Among the stilbenes examined, Pte exerted a broad-spectrum inhibitory effect on various enteroviruses, including EV-A71, EV-D68, and coxsackieviruses at 40 μM, without cytotoxicity. Mechanistically, Pte significantly inhibited enteroviral attachment, inactivated viral particles, blocked viral binding to its receptors, and increased virion stability. Molecular docking analysis revealed that Pte occupied a hydrophobic pocket in viral protein 1, indicating a strong binding affinity and acting as an efficient inhibitor. Notably, sequence alignment of multiple enteroviruses indicated that the Pte-interacting residues in VP1 were highly conserved. In vivo studies demonstrated that oral administration of Pte significantly alleviated infection symptoms and reduced mortality in hSCARB2 transgenic mice. Pte possesses potential application as a broad-efficacy antiviral drug against enteroviral infections.

紫菀芪具有广谱抗病毒活性,可靶向肠病毒衣壳,灭活病毒颗粒,阻断病毒结合,保护小鼠免受EV-A71致死性攻击。
人类肠道病毒(ev)是世界范围内的一个重大公共卫生问题,因为它们有可能引起呼吸系统疾病、手足口病和严重的神经系统并发症。目前,没有有效的药物或多价疫苗可用。紫檀芪(Pte)是一种天然存在的化合物,存在于蓝莓和其他植物中,是一种与白藜芦醇结构相似的芪。紫檀芪具有抗氧化、抗炎和抗癌的特性。然而,很少有研究探索其抗病毒活性。本研究旨在探讨Pte对EV-A71和EV-D68的抗肠道病毒作用及其机制。通过细胞毒性和抗病毒试验来评估Pte对细胞的安全性及其对肠道病毒的抗病毒作用。通过病毒附着、失活、细胞受体结合、western blotting、添加时间和去除时间、颗粒稳定性热释放、分子对接等实验来阐明Pte的抗病毒机制,并通过体内实验验证Pte的抗病毒作用。在所检测的二苯乙烯中,Pte在40 μM下对多种肠道病毒(包括EV-A71、EV-D68和柯萨奇病毒)具有广谱抑制作用,无细胞毒性。机制上,Pte显著抑制肠病毒附着,灭活病毒颗粒,阻断病毒与其受体的结合,并增加病毒粒子的稳定性。分子对接分析显示,Pte在病毒蛋白1中占据一个疏水口袋,具有较强的结合亲和力,是一种有效的抑制剂。值得注意的是,多个肠病毒的序列比对表明VP1中pte相互作用残基是高度保守的。体内研究表明,口服Pte可显著缓解hSCARB2转基因小鼠的感染症状并降低死亡率。Pte作为一种广泛有效的肠病毒感染抗病毒药物具有潜在的应用前景。
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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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