Autor(es): Ho Yi-Jung, Wang Yu-Ming, Lu Jeng-wei, Wu Tzong-Yuan, Lin Liang-In, Kuo Szu-Cheng, Lin Chang-Chi

Resumo: The mosquito-borne Chikungunya virus (CHIKV) is a profound global threat due to its high rate of contagion - 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 - to elucidate the molecular mechanism underlying inhibition using plaque reduction assay, RT-qPCR, western blot analysis, - 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 - 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, - cell-to-cell transmission. Cytopathic effect, viral RNA, viral protein, - 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 - 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 - cell-to-cell transmission of CHIKV. In conclusion, Suramin shows considerable potential as a novel anti-CHIKV agent targeting viral entry, extracellular transmission, - cell-to-cell transmission.

Imprenta: PloS One, v. 10, n. 7, p. e0133511, 2015

Identificador do objeto digital: 10.1371/journal.pone.0133511

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Transmission ; Chikungunya virus - Vaccine ; Chikungunya virus - Immunology

Data de publicação: 2015

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