In vitro synergistic antiviral activity of repurposed drugs against enterovirus 71

IF 2.5 4区医学 Q3 VIROLOGY Archives of Virology Pub Date : 2024-07-30 DOI:10.1007/s00705-024-06097-1

Kunlakanya Jitobaom, Chompunuch Boonarkart, Songkran Thongon, Thanyaporn Sirihongthong, Arpakorn Sornwong, Prasert Auewarakul, Ornpreya Suptawiwat

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Abstract

Enteroviruses cause viral diseases that are harmful to children. Hand, foot, and mouth disease (HFMD) with neurological complications is mainly caused by enterovirus 71 (EV71). Despite its clinical importance, there is no effective antiviral drug against EV71. However, several repurposed drugs have been shown to have antiviral activity against related viruses. Treatments with single drugs and two-drug combinations were performed in vitro to assess anti-EV71 activity. Three repurposed drug candidates with broad-spectrum antiviral activity were found to demonstrate potent anti-EV71 activity: prochlorperazine, niclosamide, and itraconazole. To improve antiviral activity, combinations of two drugs were tested. Niclosamide and itraconazole showed synergistic antiviral activity in Vero cells, whereas combinations of niclosamide-prochlorperazine and itraconazole-prochlorperazine showed only additive effects. Furthermore, the combination of itraconazole and prochlorperazine showed an additive effect in neuroblastoma cells. Itraconazole and prochlorperazine exert their antiviral activities by inhibiting Akt phosphorylation. Repurposing of drugs can provide a treatment solution for HFMD, and our data suggest that combining these drugs can enhance that efficacy.

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针对肠道病毒 71 的再利用药物的体外协同抗病毒活性。

肠道病毒会引起对儿童有害的病毒性疾病。伴有神经系统并发症的手足口病（HFMD）主要由肠道病毒 71 型（EV71）引起。尽管 EV71 在临床上非常重要，但目前还没有有效的抗 EV71 病毒药物。不过，几种再利用药物已被证明对相关病毒具有抗病毒活性。为了评估抗EV71病毒的活性，我们在体外进行了单药和双药联合治疗。研究发现，三种具有广谱抗病毒活性的候选药物具有很强的抗EV71活性，它们是丙氯丙嗪、烟酰胺和伊曲康唑。为了提高抗病毒活性，对两种药物的组合进行了测试。尼可刹米和伊曲康唑在 Vero 细胞中显示出协同抗病毒活性，而尼可刹米-丙氯哒嗪和伊曲康唑-丙氯哒嗪的组合仅显示出相加效应。此外，伊曲康唑和丙氯哒嗪的组合在神经母细胞瘤细胞中显示出相加效应。伊曲康唑和丙氯苯嗪通过抑制 Akt 磷酸化来发挥抗病毒作用。药物的再利用可以为手足口病提供一种治疗方案，而我们的数据表明，将这些药物联合使用可以提高疗效。

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来源期刊

Archives of Virology 医学-病毒学

CiteScore

5.10

自引率

7.40%

发文量

324

审稿时长

4.5 months

期刊介绍： Archives of Virology publishes original contributions from all branches of research on viruses, virus-like agents, and virus infections of humans, animals, plants, insects, and bacteria. Coverage spans a broad spectrum of topics, from descriptions of newly discovered viruses, to studies of virus structure, composition, and genetics, to studies of virus interactions with host cells, organisms and populations. Studies employ molecular biologic, molecular genetics, and current immunologic and epidemiologic approaches. Contents include studies on the molecular pathogenesis, pathophysiology, and genetics of virus infections in individual hosts, and studies on the molecular epidemiology of virus infections in populations. Also included are studies involving applied research such as diagnostic technology development, monoclonal antibody panel development, vaccine development, and antiviral drug development.Archives of Virology wishes to publish obituaries of recently deceased well-known virologists and leading figures in virology.