Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multistage Antimalarial Drug
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Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multistage Antimalarial Drug
| Title: | Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multistage Antimalarial Drug |
| Author: |
da Cruz, Filipa P.; Martin, Cécilie; Lafuente-Monasterio, Maria J.; Rodrigues, Tiago; Sönnichsen, Birte; Moreira, Rui; Gamo, Francisco-Javier; Hannus, Michael; Prudêncio, Miguel; Buchholz, Kathrin; Marti, Matthias; Mota, Maria
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | da Cruz, Filipa P., Cécilie Martin, Kathrin Buchholz, Maria J. Lafuente-Monasterio, Tiago Rodrigues, Birte Sönnichsen, Rui Moreira, et al. 2012. Drug screen targeted at plasmodium liver stages identifies a potent multistage antimalarial drug. The Journal of Infectious Diseases 205(8): 1278-1286. |
| Full Text & Related Files: |
3308910.pdf (804.2Kb; PDF) 
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| Abstract: | Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host’s liver cells before they are able to infect erythrocytes and cause malaria symptoms. To overcome the scarcity of compounds targeting the liver stage of malaria, we screened a library of 1037 existing drugs for their ability to inhibit Plasmodium hepatic development. Decoquinate emerged as the strongest inhibitor of Plasmodium liver stages, both in vitro and in vivo. Furthermore, decoquinate kills the parasite’s replicative blood stages and is active against developing gametocytes, the forms responsible for transmission. The drug acts by selectively and specifically inhibiting the parasite’s mitochondrial \(bc_1\) complex, with little cross-resistance with the antimalarial drug atovaquone. Oral administration of a single dose of decoquinate effectively prevents the appearance of disease, warranting its exploitation as a potent antimalarial compound. |
| Published Version: | doi:10.1093/infdis/jis184 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308910/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:8605332 |
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