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Host cdc2-like kinase 1 (CLK1) is responsible for the alteative splicing of the influenza virus M2 gene during influenza virus infection and replication that has been recognized as a potential anti-influenza virus target.In this study,we showed that gallocatechin-7-gallate (J10688),a novel CLK1 inhibitor isolated from Pithecellobium clypearia Benth,exerted potent anti-influenza virus activity in vivo and in vitro.ICR mice were intranasally infected with a lethal dose of H1N1.Administration of J10688 (30 mg.kg-1.d-1,iv,for 5 days) significantly increased the survival rate of the H1N1-infected mice to 91.67% and prolong their mean survival time from 5.83 ± 1.74 days to 13.66 ± 1.15 days.J10688 administration also slowed down body weight loss,significantly alleviated influenza-induced acute lung injury,reduced lung virus titer,elevated the spleen and thymus indexes,and enhanced the immunological function.We further explored its anti-influenza mechanisms in the H1N1-infected A549 cells:as a novel CLK1 inhibitor,J10688 (3,10,30 lμmol/L) dose-dependently impaired synthesis of the viral proteins NP and M2,and significantly downregulated the phosphorylation of splicing factors SF2/ASF and SC35,which regulate virus M2 gene alteative splicing.As a novel CLK1 inhibitor with potent anti-influenza activity in vitro and in vivo,J10688 could be a promising antiviral drug for the therapy of influenza A virus infection.