Products Cited in Publications Worldwide In Vivo Efficacy of a Broad-Spectrum Antiviral Combination Against Yellow Fever in a Hamster Model

In Vivo Efficacy of a Broad-Spectrum Antiviral Combination Against Yellow Fever in a Hamster Model

Weight, Abbie E; Stanger, Hunter; Geraghty, Robert J; Bonnac, Laurent F; Julander, Justin G

DOI:

Abstract

Yellow fever virus (YFV) recurrently causes severe outbreaks in tropical regions of South America and Africa and an average of 30 to 40 thousand deaths worldwide each year. An effective vaccine is available but the coverage of the population in countries at risk is not optimal. No are currently approved for YFV treatment. Herein, we describe the evaluation of 6-MMPr, a de-novo-purine-nucleotide biosynthesis inhibitor, as a potentiator for enhanced activity of the broad-spectrum drug in a hamster model of yellow fever. Administration of 6-MMPr was well-tolerated and a combination of and 6-MMPr did not cause overt toxicity as indicated by normal weight gain of treated hamsters. Treatment with a combination of a suboptimal dose of with 6-MMPr was significantly more effective in improving survival, weight change and virus replication when compared with monotherapy. The initiation of treatment two days after virus challenge was also effective in improving survival when compared with monotherapy. Our results demonstrate the safety and efficacy of such a combination either as a preventive or delayed treatment.

Keywords

broad-spectrum ; drug combination ; pandemic preparedness ; ; yellow fever ; flaviviruses ; animal model

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Favipiravir

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