title: In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant.
abstract: Arbidol (ARB) is an antiviral drug originally licensed in Russia for use against influenza and other respiratory viral infections. Although a broad-spectrum antiviral activity has been reported for this drug, there is until now no data regarding its effects against alphavirus infection. Here, the in vitro antiviral effect of ARB on Chikungunya virus (CHIKV) replication was investigated and this compound was found to present potent inhibitory activity against the virus propagated onto immortalized Vero cells or primary human fibroblasts (MRC-5 lung cells) (IC(50)<10μg/ml). A CHIKV resistant mutant was then selected and adapted to growth in the presence of 30μg/ml ARB in MRC5 cells; its complete sequence analysis revealed a single amino acid substitution (G407R) localized in the E2 envelope protein. To confirm the G407R role in the molecular mechanism of ARB resistance, a CHIKV infectious clone harboring the same substitution was engineered, tested, and was found to display a similar level of resistance. Finally, our results demonstrated the effective in vitro antiviral activity of ARB against CHIKV and gave some tracks to understand the molecular basis of ARB activity.
authors: Unité des Virus Emergents, UMR190 Emergence des pathologies virales Université de la Méditerranée, Institut de Recherche pour le Développement, EHSP French School of Public Health, Faculté de Médecine, Marseille, France.
authors: Ilenia
authors: I
authors: Delogu
authors: Boris
authors: B
authors: Pastorino
authors: Cécile
authors: C
authors: Baronti
authors: Antoine
authors: A
authors: Nougairède
authors: Emilie
authors: E
authors: Bonnet
authors: Xavier
authors: X
authors: de Lamballerie
mesh_terms: D018354:Alphavirus Infections / Q000188:drug therapy / Q000821:virology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D024882:Drug Resistance, Viral / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009154:Mutation; D014779:Virus Replication / Q000187:drug effects; D013440:Sulfides
chemical_list: D000998:Antiviral Agents; D007211:Indoles; C086979:umifenovir; D013440:Sulfides