Endochin-like quinolone-300 ELQ-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi

Authors: SILVA, MARTA - Washington State University; BASTOS, REGINALDO - Washington State University; STONE, DOGGET - University Of Oregon; RISCOE, MICHAEL - University Of Oregon; POU, SOVITJ - Veterans Affairs Medical Center - Portland; WINTER, ROLF - Veterans Affairs Medical Center - Portland; DODEAN, ROSALIA - Veterans Affairs Medical Center - Portland; NILSEN, AARON - Veterans Affairs Medical Center - Portland; Suarez, Carlos

Submitted to: Parasites & Vectors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2020
Publication Date: 12/3/2020
Citation: Silva, M.G., Bastos, R.G., Stone, D.J., Riscoe, M.K., Pou, S., Winter, R., Dodean, R.A., Nilsen, A., Suarez, C.E. 2020. Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi. Parasites & Vectors. 13. Article 606. https://doi.org/10.1186/s13071-020-04487-3.
DOI: https://doi.org/10.1186/s13071-020-04487-3

Interpretive Summary: The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. Endochin-like quinolones (ELQ)-300 and ELQ-316 proved safe and efficacious against related apicomplexans, such as Plasmodium spp., and ELQ 316 was also effective against B. microti, without showing toxicity in mammals. In this study we demonstrated the ability of ELQ-300 and ELQ 316 to inhibit the invitro growth of the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis

Technical Abstract: Background: The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. Endochin-like quinolones (ELQ)-300 and ELQ-316 proved safe and efficacious against related apicomplexans, such as Plasmodium spp., and ELQ-316 was also effective against B. microti, without showing toxicity in mammals. Methods: Inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. Percentage of parasitized erythrocytes was measured by flow cytometry. Effect of the ELQ drugs on the viability of actively replicating horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by ELISA. Results: We calculated IC50 ranging from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 at 72 hr among all cultured parasites tested. None of the parasites tested were able to replicate in cultures in the presence of the ELQs-300 and ELQ-316 at IC100, which range from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 hours. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing. Conclusions: ELQ-300 and ELQ-316 have a significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.