Anti-influenza drug screening and inhibition of apigetrin on influenza A virus replication via TLR4 and autophagy pathways.

Activation of Toll-like receptor (TLR) 4 plays important roles in the influenzaA virus (IAV) infection. To explore TLR4 inhibitors, 161 traditional Chinese medicines (TCMs) were screened. Further, we screened out Ixeris sonchifolia Hance, and its active compound, Apigetrin (apigenin-7-O-glucoside). Antiviral activity of Apigetrin was determined by plaque assay. We also further investigated the influence of Apigetrin on immune signaling pathways including TLRs, MAPK, NF-κB and autophagy pathways. The in-vitro results showed that the extract and its several ingredients could significantly inhibit IAV replication. Apigetrin significantly improved IAV-induced oxidative stress, inhibited the IAV-induced cytokine storm by suppressing the excessive activation of TLR3/4/7, JNK/p38 MAPK and NF-κB. Apigetrin decreased autophagosome accumulation and promoted degradation of IAV protein. Interestingly, Apigetrin antiviral activity was reversed by using H

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.