https://scholars.lib.ntu.edu.tw/handle/123456789/377241
標題: | Inhibitory and combinatorial effect of diphyllin, a v-ATPase blocker, on influenza viruses | 作者: | HUI-WEN CHEN Cheng, J.X. Liu, M.-T. King, K. Peng, J.-Y. Zhang, X.-Q. Wang, C.-H. Shresta, S. Schooley, R.T. Liu, Y.-T. |
關鍵字: | Amantadine; Diphyllin; Influenza virus; Oseltamivir; Vacuolar ATPase inhibitor | 公開日期: | 2013 | 卷: | 99 | 期: | 3 | 起(迄)頁: | 371-382 | 來源出版物: | Antiviral Research | 摘要: | An influenza pandemic poses a serious threat to humans and animals. Conventional treatments against influenza include two classes of pathogen-targeting antivirals: M2 ion channel blockers (such as amantadine) and neuraminidase inhibitors (such as oseltamivir). Examination of the mechanism of influenza viral infection has shown that endosomal acidification plays a major role in facilitating the fusion between viral and endosomal membranes. This pathway has led to investigations on vacuolar ATPase (v-ATPase) activity, whose role as a regulating factor on influenza virus replication has been verified in extensive genome-wide screenings. Blocking v-ATPase activity thus presents the opportunity to interfere with influenza viral infection by preventing the pH-dependent membrane fusion between endosomes and virions. This study aims to apply diphyllin, a natural compound shown to be as a novel v-ATPase inhibitor, as a potential antiviral for various influenza virus strains using cell-based assays. The results show that diphyllin alters cellular susceptibility to influenza viruses through the inhibition of endosomal acidification, thus interfering with downstream virus replication, including that of known drug-resistant strains. In addition, combinatorial treatment of the host-targeting diphyllin with pathogen-targeting therapeutics (oseltamivir and amantadine) demonstrates enhanced antiviral effects and cell protection in vitro. ? 2013 Elsevier B.V. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84884578114&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/377241 |
DOI: | 10.1016/j.antiviral.2013.06.014 | SDG/關鍵字: | adenosine triphosphatase; amantadine; diprophylline; oseltamivir; 1,3 benzodioxole derivative; amantadine; antivirus agent; diprophylline; enzyme inhibitor; herbaceous agent; lignan; oseltamivir; proton transporting adenosine triphosphate synthase; 1,3 benzodioxole derivative; antivirus agent; enzyme inhibitor; herbaceous agent; lignan; proton transporting adenosine triphosphate synthase; adenosine triphosphatase inhibitor; diprophylline; acidification; animal cell; antiviral activity; article; avian influenza virus; cell protection; cell viability; controlled study; cytopathogenic effect; cytotoxicity; Dengue virus 2; drug cytotoxicity; endosome; hemagglutination test; IC 50; in vitro study; infection sensitivity; influenza; Influenza virus; Influenza virus A H1N1; Influenza virus A H3N2; membrane fusion; nonhuman; pH; priority journal; protein expression; virion; virus culture; virus entry; virus replication; angiosperm; animal; chemistry; drug antagonism; drug combination; drug effect; enzymology; human; influenza; Influenza virus; metabolism; Orthomyxovirus; physiology; Vacuolar ATPase inhibitor; virology; antagonists and inhibitors; drug effects; enzymology; Influenza, Human; Orthomyxovirus; cell assay; fluorescence microscopy; real time polymerase chain reaction; Western blotting; Amantadine; Diphyllin; Influenza virus; Oseltamivir; Vacuolar ATPase inhibitor; Amantadine; Angiosperms; Animals; Antiviral Agents; Benzodioxoles; Drug Therapy, Combination; Drugs, Chinese Herbal; Endosomes; Enzyme Inhibitors; Humans; Influenza, Human; Lignans; Membrane Fusion; Orthomyxoviridae; Oseltamivir; Vacuolar Proton-Translocating ATPases; Virus Replication; Amantadine; Angiosperms; Animals; Antiviral Agents; Benzodioxoles; Drug Therapy, Combination; Drugs, Chinese Herbal; Endosomes; Enzyme Inhibitors; Humans; Influenza, Human; Lignans; Membrane Fusion; Orthomyxoviridae; Oseltamivir; Vacuolar Proton-Translocating ATPases; Virus Replication |
顯示於: | 獸醫學系 |
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