IRES-driven translation plays an essential role in picornavirus infection. However, there are seldom reports of compounds targeting this pathway with effective protection in animal models. Here, we identified emetine, an antiprotozoal drug, which inhibits EV-A71 with an EC50 value of 0.04 μM and a CC50 value of 10 μM in RD cell culture. Interestingly, emetine exhibits activities against a series of human enteroviruses, including CV-A16, CV-B1, EV-D68, Echov-6, etc., at the nanomolar level. When orally administered at 0.20 mg/kg twice a day in an EV-A71 mouse model, emetine reduced viral loads in various organs and completely prevented diseases and death. A mechanistic study demonstrated that emetine suppressed EV-A71 by inhibiting viral IRES-driven translation. Taken together, these data indicate emetine as a promising candidate to treat picornavirus infection.

中文翻译：

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Emetine通过抑制病毒翻译来保护小鼠免受肠道病毒感染。

IRES驱动的翻译在小核糖核酸病毒感染中起着至关重要的作用。然而，在动物模型中很少有针对这种途径的化合物具有有效保护的报道。在这里，我们鉴定了曲美汀，一种抗原生动物药物，在RD细胞培养中可抑制EV-A71，其EC50值为0.04μM，CC50值为10μM。有趣的是，依美替丁在纳摩尔水平上表现出针对一系列人类肠病毒的活性，包括CV-A16，CV-B1，EV-D68，Echov-6等。在EV-A71小鼠模型中，每天两次以0.20 mg / kg口服给药时，依米丁降低了各个器官的病毒载量，并完全预防了疾病和死亡。一项机理研究表明，依替米汀可通过抑制病毒IRES驱动的翻译来抑制EV-A71。在一起