Antiviral activities of Schizonepeta tenuifolia Briq. against enterovirus 71 in vitro and in vivo.

Antiviral activities of Schizonepeta tenuifolia Briq. against enterovirus 71 in vitro and in vivo.
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DOI:
10.1038/s41598-017-01110-x
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发表时间:
2017-04-20
期刊:
影响因子:
4.6
通讯作者:
Ho HY
Ho HY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen SG;Cheng ML;Chen KH;Horng JT;Liu CC;Wang SM;Sakurai H;Leu YL;Wang SD;Ho HY

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目前没有有效的药物可用于治疗肠病毒71(EV 71)感染。荆芥内酯类(ST)已被用作传统中药的草药成分。研究荆芥水提物是否具有抗病毒活性。STE抑制EV 71的复制,如通过其减少由EV 71诱导的空斑形成和细胞病变效应的能力以及抑制病毒RNA和蛋白质的合成的能力所证明的。此外,每日单剂量STE治疗显着改善EV 71感染小鼠的存活率,并改善症状。从机制上讲,STE对肠道病毒感染产生多种影响。用STE处理减少了病毒附着和进入; EV 71蛋白酶2Apro切割真核翻译起始因子4G(eIF 4G);病毒诱导的活性氧(ROS)形成;以及异质核核糖核蛋白A1(hnRNP A1)从细胞核到细胞质的重新定位。它伴随着EV 71相关的p38激酶和EPS 15的过度磷酸化的下降。STE可能抑制ROS诱导的p38激酶活化,以及随后的hnRNPA 1重新定位和受感染细胞中EPS 15介导的膜运输。这些结果表明,STE具有抗EV 71活性,可作为预防EV 71的保健食品或候选抗病毒药物。
No effective drug is currently available for treatment of enterovirus 71 (EV71) infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal constituent of traditional Chinese medicine. We studied whether the aqueous extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE inhibited replication of EV71, as evident by its ability to diminish plaque formation and cytopathic effect induced by EV71, and to inhibit the synthesis of viral RNA and protein. Moreover, daily single-dose STE treatment significantly improved the survival of EV71-infected mice, and ameliorated the symptoms. Mechanistically, STE exerts multiple effects on enteroviral infection. Treatment with STE reduced viral attachment and entry; the cleavage of eukaryotic translation initiation factor 4 G (eIF4G) by EV71 protease, 2Apro; virus-induced reactive oxygen species (ROS) formation; and relocation of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) from the nucleus to the cytoplasm. It was accompanied by a decline in EV71-associated hyperphosphorylation of p38 kinase and EPS15. It is plausible that STE may inhibit ROS-induced p38 kinase activation, and subsequent hnRNP A1 relocation and EPS15-mediated membrane trafficking in infected cells. These findings suggest that STE possesses anti-EV71 activities, and may serve as health food or candidate antiviral drug for protection against EV71.