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MMV020275 and MMV020490, promising compounds from malaria box for the treatment of equine piroplasmosis.
Abstract: Equine piroplasmosis is a tick-transmitted disease that is considered one of the most serious infectious diseases affecting equines. Searching for novel antipiroplasm drugs remains indispensable due to the emergence and spreading of resistant piroplasm parasites against the limited currently used drugs, diminazene aceturate and imidocarb dipropionate. Therefore, novel drugs with specified targets need to be identified and exploited. The inhibitory effects of Medicines for Malaria Venture (MMV) Malaria Box compounds with potent in vitro anti-equine piroplasmosis activity were evaluated against the growth of B. microti in mice in this study. Using a nested PCR assay targeting the B. microti ss-rRNA gene, we investigated the far-reaching impacts of effective combinations to inhibit parasite recrudescence. Using real-time PCR, this study revealed potential targets for the found potent compounds. When used as monotherapy, screening the Malaria Box against the in vivo growth of the B. microti parasite resulted in the discovery of new, potent antipiroplasm medicines, such as MMV020275 and MMV020490. In MMV020275-treated Theileria equi in vitro culture, a statistically significant difference (P<0.05) in the cGMP-dependent protein kinase (PKG) mRNA level was identified as a down-regulation in contrast to non-treated cultures. In conclusion, new potent antipiroplasm drugs, including MMV020275 and MMV020490 are identified. MMV020275 significantly down-regulate the mRNA levels of the PKG gene. Clofazimine enhanced the inhibitory efficacy of MMV compounds which is suggested to use in treatment of animal or human babesiosis in the future.
Copyright © 2022 Elsevier GmbH. All rights reserved.
Publication Date: 2022-01-15 PubMed ID: 35091295DOI: 10.1016/j.ttbdis.2022.101904Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
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 study focuses on the discovery of new potential drugs (MMV020275 and MMV020490) from the Malaria Box that may be effective in treating equine piroplasmosis, a disease serious to horses and caused by tick-transmitted parasites. These drugs were found to inhibit growth of parasites and lead to significant decrease in certain gene levels, providing potential for future treatments.
Understanding Equine Piroplasmosis and the Current Treatment Limitations
- Equine piroplasmosis is a major infectious disease affecting horses, transmitted by ticks and caused by parasites.
- With increasing cases of parasite resistance against commonly used drugs – diminazene aceturate and imidocarb dipropionate – the need for novel drugs becomes imperative.
- The search for newer drugs involves identifying specific targets and exploiting them to control the disease.
Investigating Medicines for Malaria Venture (MMV) Malaria Box Compounds
- The study investigated compounds from the Malaria Box for their potential effect against equine piroplasmosis.
- A nested PCR assay was deployed to inhibit parasite recrudescence – the recurrence of parasite population after a period of control.
- The study utilized real-time PCR to reveal potential targets for these potent compounds.
Identification of MMV020275 and MMV020490 as Potent Antipiroplasm Drugs
- When tested against in vivo growth of the B. microti parasite, Malaria Box screening led to identification of potent antipiroplasm drugs, MMV020275 and MMV020490.
- Significant decrease in cGMP-dependent protein kinase (PKG) mRNA level was noticed in theileria equi cultures treated with MMV020275, indicating the drug’s impact on genetic levels.
- The drastic down-regulation of the PKG gene further emphasizes on the potential of MMV020275 as a potent drug.
Enhancing Treatment Efficacy with Clofazimine
- Clofazimine, a medicinal compound, was found to enhance the inhibitory efficacy of MMV compounds.
- The future application of clofazimine along with the MMV compounds can potentially provide more effective treatments for animal or human babesiosis.
Cite This Article
APA
Rizk MA, El-Sayed SAE, Eltaysh R, Igarashi I.
(2022).
MMV020275 and MMV020490, promising compounds from malaria box for the treatment of equine piroplasmosis.
Ticks Tick Borne Dis, 13(2), 101904.
https://doi.org/10.1016/j.ttbdis.2022.101904 Publication
Researcher Affiliations
- National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido, Japan; Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Dakahlia, Egypt. Electronic address: dr_moh_abdo2008@mans.edu.eg.
- National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido, Japan; Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
- National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido, Japan; Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
- National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido, Japan. Electronic address: igarcpmi@obihiro.ac.jp.
MeSH Terms
- Animals
- Babesia / genetics
- Babesiosis / drug therapy
- Babesiosis / parasitology
- Cattle
- Horse Diseases / drug therapy
- Horse Diseases / parasitology
- Horses
- Malaria
- Mice
- Real-Time Polymerase Chain Reaction
- Theileria / genetics
- Theileriasis / parasitology
Citations
This article has been cited 6 times.- El-Sayed SAE, Rizk MA, Baghdadi HB, Ringo AE, Sambuu G, Nugraha AB, Igarashi I. Development of a promising antigenic cocktail for the global detection of Babesia caballi in horse by ELISA. PLoS One 2023;18(4):e0284535.
- Onzere CK, Hulbert M, Sears KP, Williams LBA, Fry LM. Tulathromycin and Diclazuril Lack Efficacy against Theileria haneyi, but Tulathromycin Is Not Associated with Adverse Clinical Effects in Six Treated Adult Horses. Pathogens 2023 Mar 14;12(3).
- Rizk MA, El-Sayed SAE, Igarashi I. In Vitro Inhibitory Effects and Bioinformatic Analysis of Norfloxacin and Ofloxacin on Piroplasm. Acta Parasitol 2023 Mar;68(1):213-222.
- Rizk MA, Baghdadi HB, El-Sayed SAE, Eltaysh R, Igarashi I. Repurposing of the Malaria Box for Babesia microti in mice identifies novel active scaffolds against piroplasmosis. Parasit Vectors 2022 Sep 19;15(1):329.
- Eltaysh R, Rizk MA, El-Sayed SAE, Abouelnasr K, Abdallah AA, Igarashi I. Evaluation of the in vitro and in vivo inhibitory effects of Artemisia herba-alba against the growth of piroplasm parasites. J Adv Vet Anim Res 2022 Jun;9(2):267-274.
- Cardillo NN, Villarino NF, Kappmeyer LS, Chung CJ, Suarez CE, Bastos RG. Tafenoquine succinate inhibits the growth of the equine piroplasmosis hemoparasites Theileria equi and Babesia caballi. Parasit Vectors 2026 Jan 27;19(1):61.
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