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A number of 1-methyl-1,4-dihydrotrigonellinate derivatives of ribavirin and various ribavirin esters were prepared as potential brain-targeting delivery forms. Systemic administration of a model system (1-[5′-(1-methyl-3-carbonyl-1,4-dihydropyridine)-2′,3′-bis-O-isobutyrate-β-D-ribofuranosyl]1,2,4-triazol-3-carboxamide) resulted in a significant brain concentration of the corresponding pyridinium salt. Antiviral testing accomplished with the aid of a mouse model, in which a Phlebovirus (Punta Toro virus) was intracranially inoculated, showed that while ribavirin itself was without effect, several ribavirin chemical delivery systems (CDS) exerted significant activity. These responses included increased number of survivors and increased mean survival time. It is suggested that the CDS approach may improve the efficacy of ribavirin towards various RNA viral encephalitis diseases.

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