Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Department of Central instrument and Research Laboratory, Virology and Immunology Laboratory, Chulabhorn Royal Academy, Bangkok, 10210, Thailand.
Arch Virol. 2024 Jul 30;169(8):169. doi: 10.1007/s00705-024-06097-1.
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.
肠道病毒引起的病毒性疾病对儿童有害。手足口病（HFMD）伴有神经系统并发症，主要由肠道病毒 71 型（EV71）引起。尽管具有临床重要性，但目前尚无针对 EV71 的有效抗病毒药物。然而，一些已被重新利用的药物已被证明对相关病毒具有抗病毒活性。在体外进行了单药和两药联合治疗，以评估抗 EV71 活性。发现三种具有广谱抗病毒活性的再利用药物候选物具有很强的抗 EV71 活性：丙氯拉嗪、氯硝柳胺和伊曲康唑。为了提高抗病毒活性，测试了两种药物的组合。氯硝柳胺和伊曲康唑在 Vero 细胞中显示出协同抗病毒活性，而氯硝柳胺-丙氯拉嗪和伊曲康唑-丙氯拉嗪的组合仅表现出相加作用。此外，伊曲康唑和丙氯拉嗪的组合在神经母细胞瘤细胞中表现出相加作用。伊曲康唑和丙氯拉嗪通过抑制 Akt 磷酸化发挥抗病毒作用。药物再利用可以为手足口病提供治疗方案，我们的数据表明，联合使用这些药物可以增强疗效。
