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Parasites & vectors2020; 13(1); 606; doi: 10.1186/s13071-020-04487-3

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

Abstract: 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. The endochin-like quinolones (ELQ)-300 and ELQ-316 have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp., with ELQ-316 also being effective against Babesia microti, without showing toxicity in mammals. Methods: The inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. The percentage of parasitized erythrocytes was measured by flow cytometry, and the effect of the ELQ compounds on the viability of horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by monitoring cell metabolic activity using a colorimetric assay. Results: We calculated the half maximal inhibitory concentration (IC) at 72 h, which ranged from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 among all cultured parasites tested at 72 h. None of the parasites tested were able to replicate in cultures in the presence of ELQ-300 and ELQ-316 at the maximal inhibitory concentration (IC), which ranged from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 h. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC in in vitro testing. Conclusions: The compounds ELQ-300 and ELQ-316 showed 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.
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Publication Date: 2020-12-03 PubMed ID: 33272316PubMed Central: PMC7712603DOI: 10.1186/s13071-020-04487-3Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper discusses the inhibitory effects of endochin-like quinolones, specifically ELQ-300 and ELQ-316, on parasites responsible for bovine babesiosis and equine piroplasmosis. It presents the possibility of these chemicals as effective, safer alternatives to current treatments for these diseases.

Introduction and Background

  • This paper revolves around the common apicomplexan parasites, Babesia bovis and B. bigemina, which are responsible for causing bovine babesiosis and B. caballi and Theileria equi, which cause equine piroplasmosis.
  • Chemotherapeutics, such as imidocarb diproprionate, are generally used to control and treat these diseases, but they can also bring about potential toxicity.
  • With drug-resistant parasites emerging, the need for safer and more effective drugs is being highlighted.
  • The endochin-like quinolones (ELQ)-300 and ELQ-316 have proven to be safe and effective against similar apicomplexans, like Plasmodium spp. and Babesia microti, without showing toxicity in mammals.

Research Methodology

  • The researchers assessed the inhibitory effects of ELQ-300 and ELQ-316 on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi.
  • The measurement of the percentage of parasitized erythrocytes was done by flow cytometry.
  • The viability of horse and bovine peripheral blood mononuclear cells (PBMC) was also assessed by monitoring cell metabolic activity using a colorimetric assay.

Key Findings

  • The half maximal inhibitory concentration (IC) at 72 hours ranged between 0.04 to 0.37nM for ELQ-300, and 0.002 to 0.1 nM for ELQ-316.
  • None of the parasites tested were able to replicate in the cultures in the presence of ELQ-300 and ELQ-316 at their maximum inhibitory concentration (IC).
  • Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their respective IC in in vitro tests.

Conclusion

  • The compounds ELQ-300 and ELQ-316 demonstrated significant inhibitory activity on the primary parasites that cause bovine babesiosis and equine piroplasmosis.
  • The research proposes that these ELQ drugs could be potential candidates for developing alternative treatment protocols for bovine babesiosis and equine piroplasmosis due to their harmless nature to the hosts.

Cite This Article

APA
Silva MG, Bastos RG, Stone Doggett J, Riscoe MK, Pou S, Winter R, Dodean RA, Nilsen A, Suarez CE. (2020). Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi. Parasit Vectors, 13(1), 606. https://doi.org/10.1186/s13071-020-04487-3

Publication

Parasites & vectors
ISSN: 1756-3305
NlmUniqueID: 101462774
Country: England
Language: English
Volume: 13
Issue: 1
Pages: 606
PII: 606

Researcher Affiliations

Silva, Marta G
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA. marta_silva@wsu.edu.
Bastos, Reginaldo G
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Stone Doggett, J
  • Oregon Health and Science University, 3181 SW Sam Jackson Blvd., Portland, Oregon, 97239, USA.
Riscoe, Michael K
  • Oregon Health and Science University, 3181 SW Sam Jackson Blvd., Portland, Oregon, 97239, USA.
Pou, Sovitj
  • VA Portland Health Care System, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA.
Winter, Rolf
  • VA Portland Health Care System, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA.
Dodean, Rozalia A
  • VA Portland Health Care System, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA.
Nilsen, Aaron
  • Oregon Health and Science University, 3181 SW Sam Jackson Blvd., Portland, Oregon, 97239, USA.
  • VA Portland Health Care System, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA.
Suarez, Carlos E
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA. carlos.suarez@usda.gov.
  • Animal Disease Research Unit, Agricultural Research Service, USDA, WSU, Pullman, WA, USA. carlos.suarez@usda.gov.

MeSH Terms

  • Animals
  • Antiprotozoal Agents / pharmacology
  • Babesia / drug effects
  • Babesia / growth & development
  • Babesia / physiology
  • Babesiosis / drug therapy
  • Babesiosis / parasitology
  • Erythrocytes / parasitology
  • Horse Diseases / drug therapy
  • Horse Diseases / parasitology
  • Horses
  • Leukocytes, Mononuclear / parasitology
  • Quinolones / pharmacology
  • Theileria / drug effects
  • Theileria / growth & development
  • Theileria / physiology
  • Theileriasis / drug therapy
  • Theileriasis / parasitology

Grant Funding

  • I01 BX001421 / BLRD VA
  • AI100569 / NIH HHS
  • I01 BX004522 / BLRD VA
  • I01 BX003312 / BLRD VA
  • R56 AI100569 / NIAID NIH HHS
  • BX004522 / U.S. Department of Veterans Affairs (US)
  • PR181134 / U.S. Department of Defense
  • 14S-RCS001 / VA Research
  • R01 AI141412 / NIAID NIH HHS
  • R01 AI100569 / NIAID NIH HHS
  • R01AI141412 / National Institute of Allergy and Infectious Diseases
  • IK2 BX002440 / BLRD VA
  • 108525-001 / International Development Research Centre
  • IK6 BX004857 / BLRD VA
  • 2090-32000-039-00D / Agricultural Research Service
  • BX002440 / U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development
  • i01 BX003312 / BLRD VA

Conflict of Interest Statement

The authors declare that they have no competing interests.

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