Human enterovirus 71 (EV71) is the second most common cause of hand, foot, and mouth disease (HFMD), which can occur as a severe epidemic especially among children under 5-years old. New and improved treatment strategies to control EV71 infection are therefore urgently required. The heterocyclic compound GS-9620, a potent and selective agonist of Toll-like receptor 7 (TLR7), has been reported to activate plasmacytoid dendritic cells (pDCs), and suppress HBV as well as HIV replication. In this study, we indicated that GS-9620 also could inhibit EV71 replication in the mouse model of EV71 infection. With three-days treatment after EV71 infection, the levels of proinflammatory cytokines/chemokines, like IFN-α, IFN-γ and MCP-1, were sharply reduced in serum compared to those without treatment. Furthermore, GS-9620 activated TLR7 in the limb muscle cells, which stimulated the NF-κB and PI3K/AKT signaling pathways. When NF-κB or PI3K/AKT inhibitors were used, the antiviral effect of the GS-9620 was impacted. Overall, our data implied GS-9620 probably activates NF-κB and PI3K/AKT signaling pathways to clear the virus.

人肠道病毒71（EV71）是手足口病（HFMD）的第二大常见病因，尤其是在5岁以下的儿童中，它可以作为一种严重的流行病而发生。因此，迫切需要新的和改进的治疗策略来控制EV71感染。据报道，杂环化合物GS-9620是Toll样受体7（TLR7）的强效选择性激动剂，可激活浆细胞样树突状细胞（pDC），并抑制HBV和HIV复制。在这项研究中，我们表明GS-9620还可以在EV71感染的小鼠模型中抑制EV71复制。与未治疗的患者相比，EV71感染后经过三天的治疗，血清中促炎性细胞因子/趋化因子（如IFN-α，IFN-γ和MCP-1）的水平急剧降低。此外，GS-9620激活了肢体肌肉细胞中的TLR7，从而刺激了NF-κB和PI3K / AKT信号通路。当使用NF-κB或PI3K / AKT抑制剂时，GS-9620的抗病毒作用受到影响。总体而言，我们的数据暗示GS-9620可能会激活NF-κB和PI3K / AKT信号通路来清除病毒。