Preprint Article Version 1 This version is not peer-reviewed

The Combination of Buparvaquone and ELQ316 Exhibits a Stronger Synergistic Effect Compared to the Combination of ELQ316 with Imidocarb, on the Survival of Babesia bovis in In Vitro Cultures

Version 1 : Received: 27 September 2024 / Approved: 29 September 2024 / Online: 30 September 2024 (12:26:27 CEST)

How to cite: Cardillo, N. M.; Villarino, N. F.; Lacy, P. A.; Riscoe, M. K.; Doggett, J. S.; Ueti, M. W.; Chung, C. J.; Suarez, C. E. The Combination of Buparvaquone and ELQ316 Exhibits a Stronger Synergistic Effect Compared to the Combination of ELQ316 with Imidocarb, on the Survival of Babesia bovis in In Vitro Cultures. Preprints 2024, 2024092385. https://doi.org/10.20944/preprints202409.2385.v1 Cardillo, N. M.; Villarino, N. F.; Lacy, P. A.; Riscoe, M. K.; Doggett, J. S.; Ueti, M. W.; Chung, C. J.; Suarez, C. E. The Combination of Buparvaquone and ELQ316 Exhibits a Stronger Synergistic Effect Compared to the Combination of ELQ316 with Imidocarb, on the Survival of Babesia bovis in In Vitro Cultures. Preprints 2024, 2024092385. https://doi.org/10.20944/preprints202409.2385.v1

Abstract

Background/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome bc1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp. and Babesia microti, without showing toxicity in mammals. The objectives of this study are investigating whether ELQ-316, BPQ and their combination treatment could be effective against Babesia bovis in an in vitro culture model, and comparing with imidocarb (ID), the routinely used drug. Methods: In vitro cultured parasites at starting 2% percentage of parasitemia (PPE) were treated with BPQ, ELQ-316, ID, and the combinations of BPQ+ ELQ-316 and ID+ ELQ-316 at drug concentrations that ranged from 25 to 1200 nM, during four consecutive days. Parasitemia levels were evaluated daily using microscopic examination. Data was compared using the independent Student's t-test and ANOVA test. Results: All drugs tested, whether used alone or in combination, significantly decreased the survival (p<0.05) of B. bovis in in vitro cultures. The combination of BPQ+ ELQ-316 had the lowest calculated inhibitory concentration 50 (IC50) 31.21 nM (IC95%: 15.06 - 68.48) values, followed by BPQ, 77.06 nM (IC95%: 70.16- 86.01), ID+ELQ316 197 nM (IC95%:129.0 - 311.2), ID 635.1 nM (IC95%: 280.9 – 2119) and ELQ316 654.9 nM (IC95%: 362.3 – 1411). Conclusion: The results reinforce the higher efficacy of BPQ at affecting B. bovis survival, and the potential synergistic effects of its combination with ELQ-316, providing a promising treatment option against B. bovis.

Keywords

apicomplexa; treatment; cytocrome; new drugs; IC50

Subject

Medicine and Pharmacology, Veterinary Medicine

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