Abstract
Ethnopharmacological relevance: Ko-Ken Tang (KKT, aka kakkon-to), a conventional Chinese herbal medicine, has been used for the treatment of common cold, fever and influenza virus infection. However, the underlying mechanism against influenza virus infection still remains elusive. Aim of study: To investigate the functional mechanism of KKT against influenza virus infection. Materials and methods: the anti-influenza virus activity and cytotoxicity effect of KKT on Madin-Darby canine kidney cells was determined. Mode of action and inhibition of viral polymerase activity was measured by time-of-addition assay and by primer extension assay, respectively. Inhibition of virus-induced phosphatidylinositol 3-kinase (PI3K)/Akt pathway by KKT was analyzed by western blotting. Inhibition of nuclear export of viral ribonucleoprotein complex by KKT was determined by indirect immunofluorescence microscopy and heterokaryon assay. Results: These data demonstrate that KKT inhibited influenza virus at the replication but not entry stage and it exhibits a broad inhibition spectrum against human influenza viruses A. KKT not only blocked virus-induced Akt phosphorylation which causes retention of viral nucleoprotein (NP) in the nucleus to interfere with virus propagation.
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