https://scholars.lib.ntu.edu.tw/handle/123456789/502672
標題: | Suramin inhibits chikungunya virus entry and transmission | 作者: | Ho Y.-J. Wang Y.-M. Lu J.-W. Wu T.-Y. LIANG-IN LIN Kuo S.-C. Lin C.-C. |
公開日期: | 2015 | 卷: | 10 | 期: | 7 | 起(迄)頁: | e0133511 | 來源出版物: | PLoS ONE | 摘要: | The mosquito-borne Chikungunya virus (CHIKV) is a profound global threat due to its high rate of contagion and the lack of vaccine or effective treatment. Suramin is a symmetric polyanionic naphthylurea that is widely used in the clinical treatment of parasite infections. Numerous studies have reported the broad antiviral activities of suramin; however, inhibition effects against CHIKV have not yet been demonstrated. The aim of this study was thus to investigate the antiviral effect of suramin on CHIKV infection and to elucidate the molecular mechanism underlying inhibition using plaque reduction assay, RT-qPCR, western blot analysis, and plaque assay. Microneutralization assay was used to determine the EC50 of suramin in the CHIKV-S27 strain as well as in three other clinical strains (0611aTw, 0810bTw and 0706aTw). Time-of-addition was used to reveal the anti-CHIKV mechanism of suramin.We also evaluated anti-CHIKV activity with regard to viral entry, virus release, and cell-to-cell transmission. Cytopathic effect, viral RNA, viral protein, and the virus yield of CHIKV infection were shown to diminish in the presence of suramin in a dose-dependent manner. Suramin was also shown the inhibitory activities of the three clinical isolates. Suramin inhibited the early progression of CHIKV infection, due perhaps to interference with virus fusion and binding, which subsequently prevented viral entry. Results of a molecular docking simulation indicate that suramin may embed within the cavity of the E1/E2 heterodimer to interfere with their function. Suramin was also shown to reduce viral release and cellto- cell transmission of CHIKV. In conclusion, Suramin shows considerable potential as a novel anti-CHIKV agent targeting viral entry, extracellular transmission, and cell-to-cell transmission. ? 2015 Ho et al. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/502672 | ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0133511 | SDG/關鍵字: | suramin; virus glycoprotein; virus protein; virus RNA; antivirus agent; suramin; virus envelope protein; animal cell; animal experiment; antiviral activity; Article; Chikungunya virus; concentration response; controlled study; cytopathogenic effect; drug structure; embryo; molecular docking; nonhuman; quantitative analysis; reverse transcription polymerase chain reaction; virus attachment; virus entry; virus release; virus strain; virus transmission; Western blotting; animal; cell line; chemical structure; chemistry; chikungunya; conformation; drug effects; metabolism; physiology; viral plaque assay; virology; Animals; Antiviral Agents; Cell Line; Chikungunya Fever; Chikungunya virus; Models, Molecular; Molecular Conformation; Suramin; Viral Envelope Proteins; Viral Plaque Assay; Virus Internalization; Virus Release |
顯示於: | 醫學檢驗暨生物技術學系 |
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