Document Type

Article

Journal/Book Title/Conference

Pathogens

Volume

14

Issue

9

Publisher

MDPI AG

Publication Date

9-12-2025

Journal Article Version

Version of Record

First Page

1

Last Page

9

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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 antivirals 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 antiviral drug favipiravir in a hamster model of yellow fever. Administration of 6-MMPr was well-tolerated and a combination of favipiravir 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 favipiravir 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.

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