In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant
Autor(es): Delogu Ilenia, Pastorino Boris, Baronti Cécile, Nougairède Antoine, Bonnet Emilie, de Lamballerie Xavier
Resumo: Arbidol (ARB) is an antiviral drug originally licensed in Russia for use against influenza - 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 - 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)<10?g/ml). A CHIKV resistant mutant was then selected - adapted to growth in the presence of 30?g/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, - was found to display a similar level of resistance. Finally, our results demonstrated the effective in vitro antiviral activity of ARB against CHIKV - gave some tracks to underst- the molecular basis of ARB activity.
Palavras-Chave: Chikungunya virus; Arbidol; Antiviral; Alphavirus; Arbidol resistance; Mutant
Imprenta: Antiviral Research, v. 90, n. 3, p. 99-107, 2011
Identificador do objeto digital: 10.1016/j.antiviral.2011.03.182
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Public health
Data de publicação: 2011
