Enterovirus D68 (EV-D68) is a member of the Picornavirus family and a causative agent of respiratory diseases in children. The incidence of EV-D68 infection has increased worldwide in recent years. Thus far, there are no approved antiviral agents or vaccines for EV-D68. Here, we show that methyl-β-cyclodextrin (MβCD), a common drug that disrupts lipid rafts, specifically inhibits EV-D68 infection without producing significant cytotoxicity at virucidal concentrations. The addition of exogenous cholesterol attenuated the anti-EV-D68 activity of MβCD. MβCD treatment had a weak influence on the attachment of viral particles to the cell membrane but significantly inhibited EV-D68 entry into host cells. We demonstrated that EV-D68 facilitated the translocation of the viral receptor ICAM-5 to membrane rafts in infected cells. The colocalization of viral particles with ICAM-5 in lipid rafts was thoroughly abolished in cells after treatment with MβCD. Finally, we showed that MβCD inhibited the replication of isolated circulating EV-D68 strains. In summary, our results demonstrate that MβCD suppresses EV-D68 replication by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts. This mechanism represents a promising strategy for drug development.

中文翻译：

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甲基-β-环糊精通过扰动脂质筏中病毒颗粒和ICAM-5的积累来抑制EV-D68病毒的进入。

肠道病毒D68（EV-D68）是小核糖核酸病毒家族的成员，是儿童呼吸系统疾病的病原体。近年来，EV-D68感染的发生率在全球范围内有所增加。到目前为止，还没有批准的EV-D68抗病毒药或疫苗。在这里，我们显示了甲基-β-环糊精（MβCD），一种破坏脂质筏的常见药物，特异性抑制EV-D68感染，而在杀病毒浓度下不会产生明显的细胞毒性。外源胆固醇的添加减弱了MβCD的抗EV-D68活性。MβCD处理对病毒颗粒附着于细胞膜的影响较弱，但显着抑制了EV-D68进入宿主细胞。我们证明，EV-D68有助于病毒受体ICAM-5易位到感染细胞的膜筏中。用MβCD处理后，在细胞中脂质体中ICAM-5与病毒颗粒的共定位被彻底消除。最后，我们表明MβCD抑制了分离的循环EV-D68菌株的复制。总之，我们的结果表明，MβCD通过扰动脂质筏中病毒颗粒和ICAM-5的积累来抑制EV-D68复制。这种机制代表了一种有前途的药物开发策略。