Anti-influenza effect and action mechanisms of the chemical constituent gallocatechin-7-gallate from Pithecellobium clypearia Benth

• 来源期刊: 中国药理学报（英文版）
• 关键词: influenza virus cdc2-like kinase 1 gallocatechin-7-gallate Pithecellobium clypearia Benth traditional Chinese medicine
• 年，卷（期）: 2018,（12）
• 页码范围: 1913-1922
• 页数: 10页
• 语种: 英文

摘要

Host cdc2-like kinase 1 (CLK1) is responsible for the alternative 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 alternative 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.