Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever

Simple item page
cg.authorship.typesCGIAR and advanced research instituteen_US
cg.contributor.affiliationInternational Livestock Research Instituteen_US
cg.contributor.affiliationWageningen University & Researchen_US
cg.contributor.crpLivestocken_US
cg.contributor.donorNorman Borlaug Commemorative Research Initiativeen_US
cg.contributor.donorUnited States Agency for International Developmenten_US
cg.contributor.donorDepartment for International Development, United Kingdomen_US
cg.contributor.donorBill & Melinda Gates Foundationen_US
cg.coverage.regionAfricaen_US
cg.coverage.regionEastern Africaen_US
cg.creator.identifierVishvanath Nene: 0000-0001-7066-4169en_US
cg.creator.identifierRoger Pelle: 0000-0003-1053-085Xen_US
cg.creator.identifierNicholas Svitek: 0000-0002-4539-5806en_US
cg.howPublishedFormally Publisheden_US
cg.identifier.doihttps://doi.org/10.1016/j.ijpddr.2019.01.002en_US
cg.isijournalISI Journalen_US
cg.issn2211-3207en_US
cg.journalInternational Journal for Parasitologyen_US
cg.reviewStatusPeer Reviewen_US
cg.speciesTheileria parvaen_US
cg.subject.ilriANIMAL DISEASESen_US
cg.subject.ilriCATTLEen_US
cg.subject.ilriDISEASE CONTROLen_US
cg.subject.ilriECFen_US
cg.subject.ilriLIVESTOCKen_US
cg.subject.ilriVACCINESen_US
cg.volume9en_US
dc.contributor.authorNyagwange, Jamesen_US
dc.contributor.authorAwino, Eliasen_US
dc.contributor.authorTijhaar, Edwinen_US
dc.contributor.authorSvitek, Nicholasen_US
dc.contributor.authorPelle, Rogeren_US
dc.contributor.authorNene, Vishvanath M.en_US
dc.date.accessioned2019-02-21T13:23:31Zen_US
dc.date.available2019-02-21T13:23:31Zen_US
dc.identifier.urihttps://hdl.handle.net/10568/99526en_US
dc.titleLeveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast feveren_US
dcterms.abstractChemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis, caused by the related parasite Theileria annulata. Recently, drug resistance was reported in T. annulata, and could occur in T. parva. Using a 3H-thymidine incorporation assay we screened 796 open source compounds from the Medicines for Malaria Venture (MMV) to discover novel chemicals with potential inhibitory activity to T. parva. We identified nine malaria box compounds and eight pathogen box compounds that inhibited the proliferation of F100TpM, a T. parva infected lymphocyte cell line. However, only two compounds, MMV008212 and MMV688372 represent promising leads with IC50 values of 0.78 and 0.61 μM, respectively, and CC50 values > 5 μM. The remaining compounds exhibited a high degree of toxicity (CC50 values < 1.09 μM) on the proliferation of bovine peripheral blood mononuclear cells stimulated with concanavalin A. We also tested the anti-cancer drug, dasatinib, used in the chemotherapy of some leukemias. Dasatinib was as active and safe as buparvaquone in vitro, with an IC50 of 5 and 4.2 nM, respectively, and CC50 > 10 μM. Our preliminary data suggest that it may be possible to repurpose compounds from the cancer field as well as MMV as novel anti-T. parva molecules.en_US
dcterms.accessRightsOpen Accessen_US
dcterms.audienceScientistsen_US
dcterms.bibliographicCitationNyagwange, J., Awino, E., Tijhaar, E., Svitek, N., Pelle, R. and Nene, V. 2019. Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever. International Journal for Parasitology: Drugs and Drug Resistance 9:80-86.en_US
dcterms.extentp. 80-86en_US
dcterms.issued2019-04en_US
dcterms.languageenen_US
dcterms.licenseCC-BY-4.0en_US
dcterms.publisherElsevieren_US
dcterms.subjecttheileriaen_US
dcterms.subjectcattleen_US
dcterms.subjectanimal diseasesen_US
dcterms.subjectvaccinesen_US
dcterms.subjectdisease controlen_US
dcterms.subjecteast coast feveren_US
dcterms.typeJournal Articleen_US

Files

License bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.75 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

ILRI articles in journals
CRP Livestock health flagship
CRP Livestock journal articles
ILRI animal and human health program outputs (2017-2024)
ILRI BecA outputs
Improved vaccines for the control of East Coast fever in cattle in Africa