Enterovirus 71, as one of the dominant pathogens associated with severe hand, foot, and mouth disease, has been well reported to trigger severe neurological symptoms among young children over the last decade, particularly among children in the Asia-Pacific region. To date, no effective antiviral agent has been developed for the treatment of severe enterovirus 71 infection. PNU-282987, a selective alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist, has been reported to have a neuroprotective effect by participating in inflammatory regulation in previous studies. Therefore, in the present study, we aimed to assess the cell-protective effect of PNU-282987 against enterovirus 71 infection in neuronal cells, and to discuss potential mechanisms underlying this cell-protective effect in order to elucidate the potential impact of such agonists in the treatment of neurotropic viral infection. We observed that treatment with PNU-282987 improved cell viability and inhibited viral replication in enterovirus 71-infected SH-SY5Y cells. Further investigation revealed that inhibition of enterovirus 71 production by PNU-282987 is likely associated with events of RNA replication, and that increased levels of INF mRNA and its downstream antiviral proteins stimulated by the JAK-STAT2 pathway may contribute to the antiviral effect of PNU-282987. Moreover, our findings suggest that both the antiviral and anti-inflammatory effects of PNU-282987 may contribute to the neural protective effect of the drug in enterovirus 71-infected cells. Taken together, the results suggest that selective α7nAChR agonists may represent viable candidates for future therapeutic treatment of severe enterovirus 71 infection, and for other cases of neurotropic viral infection.

肠道病毒71是与严重的手足口病有关的主要病原体之一，据报道，过去十年来，肠病毒71引发严重的神经系统症状，尤其是在亚太地区的儿童中。迄今为止，尚未开发出用于治疗严重肠病毒71感染的有效抗病毒剂。在先前的研究中，据报道PNU-282987是一种选择性的α7烟碱乙酰胆碱受体（α7nAChR）激动剂，具有神经保护作用。因此，在本研究中，我们旨在评估PNU-282987对神经元细胞中肠道病毒71感染的细胞保护作用，并讨论了这种细胞保护作用的潜在机制，以阐明此类激动剂在治疗嗜神经性病毒感染中的潜在作用。我们观察到，在肠道病毒71感染的SH-SY5Y细胞中，用PNU-282987进行的治疗改善了细胞活力并抑制了病毒复制。进一步的研究表明，PNU-282987对肠道病毒71产生的抑制作用可能与RNA复制事件有关，并且PNU-282987的水平升高JAK-STAT2途径刺激的INF mRNA及其下游抗病毒蛋白可能有助于PNU-282987的抗病毒作用。此外，我们的发现表明，PNU-282987的抗病毒和抗炎作用均可能有助于该药物在肠道病毒71感染的细胞中的神经保护作用。两者合计，结果表明选择性的α7nAChR激动剂可能代表严重肠病毒71感染和其他神经营养性病毒感染的未来治疗可行的候选人。