title: Suramin Inhibits Chikungunya Virus Entry and Transmission.
abstract: 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 cell-to-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.
authors.affiliation: Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Jung
authors.initials: YJ
authors.lastname: Ho
authors.affiliation: Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Jeng-wei
authors.initials: JW
authors.lastname: Lu
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan.
authors.forename: Tzong-Yuan
authors.initials: TY
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.affiliation: Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pathology, and Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Szu-Cheng
authors.initials: SC
authors.lastname: Kuo
authors.affiliation: Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chang-Chi
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D065632:Chikungunya Fever / Q000821:virology*; D002646:Chikungunya virus / Q000502:physiology*; D008958:Models, Molecular; D008968:Molecular Conformation; D013498:Suramin / Q000737:chemistry / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism; D010948:Viral Plaque Assay; D053586:Virus Internalization / Q000187:drug effects*; D057074:Virus Release / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D014759:Viral Envelope Proteins; D013498:Suramin