In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination.
Chikungunya virus (CHIKV) and Semliki Forest virus (SFV) were used in our laboratory to screen active antiviral compounds against viruses of the Alphavirus genus. Antiviral activity was estimated by the reduction of the cytopathic effect of each alphavirus on infected Vero cells and by virus titer reduction. Cytotoxicity was evaluated by determining the inhibition of Trypan blue exclusion in confluent cell cultures and by the evaluation of the inhibitory effect on cell growth. With CHIKV and SFV, the selectivity indices of human recombinant interferon-alpha and iota-carrageenan were much higher than that of ribavirin, which has been previously investigated for its inhibitory effect on alphavirus infections. Compared to ribavirin, 6-azauridine was more effective against CHIKV and showed a similar antiviral activity against SFV. IFN-alpha2b, glycyrrhizin, 6-azauridine, and ribavirin caused a concentration-dependent reduction in the virus yield with CHIKV and SFV. Moreover, the combination of IFN-alpha2b and ribavirin had a subsynergistic antiviral effect on these two alphaviruses and should be evaluated for the treatment of these infections.
Briolant
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S
Département de biologie des agents transmissibles, Centre de Recherches du Service de Santé des Armées, BP 87, 24, av. des Maquis du Grésivaudan, 38702 Cedex, La Tronche, France. daniel.garin@wanadoo.fr
Garin
D
D
Scaramozzino
N
N
Jouan
A
A
Crance
J M
JM
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D001380:Azauridine / Q000008:administration & dosage; D002646:Chikungunya virus / Q000187:drug effects* / Q000502:physiology; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004357:Drug Synergism; D019695:Glycyrrhizic Acid / Q000008:administration & dosage; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D012672:Semliki forest virus / Q000187:drug effects* / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin; D019695:Glycyrrhizic Acid; D001380:Azauridine