| Summary: | 博士 === 長庚大學 === 生物醫學研究所 === 101 === We investigated anti-influenza mechanism of two Chinese herbal decoctions: Ma-xing-shi-gan-tang (MXSGT, aka maxing shigan powder) and Ching-fang-pai-tu-san (CFPTS). MXSGT and CFPTS were traditionally used as a cure for the common cold, fever and headache. However, no studies have investigated the mode of action of MXSGT and CFPTS against influenza virus infection. The antiviral activity of nontoxic concentrations of MXSGT and CFPTS against influenza virus A/WSN/33 were examined by assaying inhibition of the virus-induced cytopathic effects (neutralization assay). The mode of MXSGT and CFPTS action were first examined with a time-of-addition assay of synchronized infections, followed by viral attachment and penetration assays. We also performed assays related to the inhibition of viral entry, such as neuraminidase (NA) activity, hemagglutinin (HA) activity, and phosphoinositide-3-kinase (PI3K)/AKT phosphorylation assays. The surface ultrastructure of the MXSGT or CFPTS-treated virus was revealed by atomic force microscopy. The synthesis of both viral RNA and protein was profoundly inhibited when the cells were treated with MXSGT. The time-of-addition assay demonstrated that MXSGT blocks the virus entry phase. High-resolution images and quantitative measurements made with atomic force microscopy confirmed that the viral surface structure was disrupted by MXSGT. We also established that viral entry, regulated by the PI3K/AKT signaling pathway, was abolished by MXSGT. These results give scientific support to the use of MXSGT in the treatment of influenza virus infections. CFPTS did not suppress viral RNA or protein synthesis. According to a time-of-addition assay, the antiviral mechanism of CFPTS may involve viral budding or viral glycoprotein exocytosis. A plaque reduction assay showed that CFPTS reduced both the plaque size and plaque quantity. The secretion of viral glycoprotein hemagglutinin was blocked by CFPTS by immunofluorescence microscopic analysis.
Therefore, the antiviral mechanism of CFPTS may inhibit the assembly of progeny virions and their subsequent release. Collectively, my studies suggest that MXSGT and CFPTS have potential utility in the management of seasonal pandemics of influenza virus infections, like other clinically available drugs, for example Tamiflu.
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