Pyronaridine combined with diminazene aceturate inhibits Babesia in vitro and in vivo

Abstract

Objective: To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo. Methods: Bioinformatic analysis was performed using atom pair fingerprints. An in vitro combination test was performed against Babesia bovis and Theileria equi. Moreover, the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay. Results: Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights. The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi. In addition, 5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment. The combination therapy also normalized the hematological parameters of infected mice. Conclusions: An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice, suggesting it might be a new paradigm for the treatment of babesiosis.

Keywords

Babesia / Pyronaridine tetraphosphate / Diminazene aceturate / Babesiosis / Theileria

Acknowledgments

The authors would like to great thank Prof. Naoaki Yokoyama, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan for his scientific support and discussion.

Conflict of interest statement

The authors declare that they have no competing interests.

Funding

This research work is supported by Deputyship for Research &Innovation, Ministry of Education in Saudi Arabia through the project number: ISP23-73.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

MAR and II supervised and designed the study. MAR, and SAESES performed experimental analysis. MZSA, MSA, SAA, N. Alsadaan, N. Alam, and SAESES performed the analytic calculation. MAR, MZSA, and II provided the resources. MAR, SAESES, MSA contributed to the final version of the manuscript. MAR and II supervised the project.

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