tetano
Editor, Senior Moderator
Acta Pharmacol Sin. 2018 May 25. doi: 10.1038/s41401-018-0030-x. [Epub ahead of print]
[h=1]Anti-influenza effect and action mechanisms of the chemical constituent gallocatechin-7-gallate from Pithecellobium clypearia Benth.[/h] Li C[SUP]1,[/SUP][SUP]2[/SUP], Xu LJ[SUP]1[/SUP], Lian WW[SUP]1[/SUP], Pang XC[SUP]1[/SUP], Jia H[SUP]1[/SUP], Liu AL[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Du GH[SUP]6,[/SUP][SUP]7,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]-[/SUP][SUP]1[/SUP]?d[SUP]-1[/SUP], 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 μmol/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.
[h=4]KEYWORDS:[/h] Pithecellobium clypearia Benth; cdc2-like kinase 1; gallocatechin-7-gallate; influenza virus; traditional Chinese medicine
PMID: 29802302 DOI: 10.1038/s41401-018-0030-x
[h=1]Anti-influenza effect and action mechanisms of the chemical constituent gallocatechin-7-gallate from Pithecellobium clypearia Benth.[/h] Li C[SUP]1,[/SUP][SUP]2[/SUP], Xu LJ[SUP]1[/SUP], Lian WW[SUP]1[/SUP], Pang XC[SUP]1[/SUP], Jia H[SUP]1[/SUP], Liu AL[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Du GH[SUP]6,[/SUP][SUP]7,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]-[/SUP][SUP]1[/SUP]?d[SUP]-1[/SUP], 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 μmol/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.
[h=4]KEYWORDS:[/h] Pithecellobium clypearia Benth; cdc2-like kinase 1; gallocatechin-7-gallate; influenza virus; traditional Chinese medicine
PMID: 29802302 DOI: 10.1038/s41401-018-0030-x