2. Academic Validation
  3. GS-9620 inhibits enterovirus 71 replication mainly through the NF-κB and PI3K-AKT signaling pathways

GS-9620 inhibits enterovirus 71 replication mainly through the NF-κB and PI3K-AKT signaling pathways

  • Antiviral Res. 2018 May;153:39-48. doi: 10.1016/j.antiviral.2018.02.002.
Qian Zhang 1,  Binbin Zhao 1,  Xin Chen 1,  Nan Song 1,  Jing Wu 1,  Guangchao Li 1,  Pin Yu 1,  Yunlin Han 1,  Jiangning Liu 2,  Chuan Qin 3
Affiliations

Affiliations

  • 1 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC) & Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Key Laboratory of Human Disease Comparative Medicine Ministry of Health, Beijing, PR China.
  • 2 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC) & Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Key Laboratory of Human Disease Comparative Medicine Ministry of Health, Beijing, PR China. Electronic address: [email protected].
  • 3 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC) & Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Key Laboratory of Human Disease Comparative Medicine Ministry of Health, Beijing, PR China. Electronic address: [email protected].
PMID: 29425831 DOI: 10.1016/j.antiviral.2018.02.002
Abstract

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.

Keywords

Enterovirus 71; Foot and mouth disease; GS-9620; Hand; NF-κB and PI3K-AKT signaling pathways.

Figures
Products