EV71是引起重症手足口病的主要病原体，目前其尚无有效治疗药物。最新研究表明，在EV71感染细胞后，TLR7与HRS形成复合物，该复合物作为信号分子，能激活NF-κB信号通路，引发细胞因子风暴。而申请人前期发现TLR7激动剂GS-9620可通过减弱NF-κB信号通路发挥抗EV71作用，提高了EV71感染小鼠的生存率；并在细胞水平上发现GS-9620能抑制HRS/TLR7复合物形成。基于此，申请人认为GS-9620可能通过抑制HRS/TLR7复合物的形成，减弱NF-κB信号通路，发挥抗EV71感染的作用。为验证该假说，拟利用免疫共沉淀、构建小鼠模型等方法，在动物水平上分析GS-9620对HRS/TLR7复合物形成和NF-κB信号通路活性的影响，以及HRS/TLR7复合物对NF-κB信号通路的调控作用。研究结果将为GS-9620的临床应用提供理论基础，将为新一代高效抗EV71药物提供新视角。

Enterovirus 71 is the main pathogen causing severe hand, foot and mouth disease, and there is currently no effective treatment. Recent studies have shown that after EV71-infected cells, toll-like receptors 7 (TLR7) forms a complex with hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), which acts as a signaling molecule that activates the NF-κB signaling pathway and triggers cytokine storms. The applicants found that the TLR7 agonist GS-9620 can enhance the survival rate of EV71-infected mice by attenuating the NF-κB signaling pathway and inhibiting the HRS/TLR7 complex at the cellular level. form. Based on this, Applicants believe that GS-9620 may attenuate NF-κB signaling pathway by inhibiting the formation of HRS/TLR7 complex and exert anti-EV71 infection. To validate this hypothesis, it is proposed to analyze the effects of GS-9620 on HRS/TLR7 complex formation and NF-κB signaling pathway activity and the HRS/TLR7 complex pair at the animal level by means of co-immunoprecipitation and mouse model construction. Regulation of the NF-κB signaling pathway. The results will provide a theoretical basis for the clinical application of GS-9620 and will provide a new perspective for a new generation of highly effective anti-EV71 drugs.