title: Assessment of flavaglines as potential chikungunya virus entry inhibitors.
abstract: Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that recently caused large epidemics in islands in, and countries around, the Indian Ocean. There is currently no specific drug for therapeutic treatment or for use as a prophylactic agent against infection and no commercially available vaccine. Prohibitin has been identified as a receptor protein used by chikungunya virus to enter mammalian cells. Recently, synthetic sulfonyl amidines and flavaglines (FLs), a class of naturally occurring plant compounds with potent anti-cancer and cytoprotective and neuroprotective activities, have been shown to interact directly with prohibitin. This study therefore sought to determine whether three prohibitin ligands (sulfonyl amidine 1 m and the flavaglines FL3 and FL23) were able to inhibit CHIKV infection of mammalian Hek293T/17 cells. All three compounds inhibited infection and reduced virus production when cells were treated before infection but not when added after infection. Pretreatment of cells for only 15 minutes prior to infection followed by washing out of the compound resulted in significant inhibition of entry and virus production. These results suggest that further investigation of prohibitin ligands as potential Chikungunya virus entry inhibitors is warranted.
authors: Institute of Molecular Biosciences, Mahidol University, Nakorn Pathom, Thailand.
authors: Phitchayapak
authors: P
authors: Wintachai
authors: Frédéric
authors: F
authors: Thuaud
authors: Christine
authors: C
authors: Basmadjian
authors: Sittiruk
authors: S
authors: Roytrakul
authors: Sukathida
authors: S
authors: Ubol
authors: Laurent
authors: L
authors: Désaubry
authors: Duncan R
authors: DR
authors: Smith
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000494:pharmacology*; D065632:Chikungunya Fever / Q000821:virology*; D002646:Chikungunya virus / Q000187:drug effects* / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D006801:Humans; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001572:Benzofurans
keywords: Chikungunya virus; entry inhibitor; flavaglines; sulfonyl amidines
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