CRIMALDDI: platform technologies and novel anti-malarial drug targets
Autor: | Donatella Taramelli, Steve A. Ward, Christian Doerig, Henri Vial, Ian C Boulton, Kelly Chibale |
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Přispěvatelé: | Department of Chemistry, Faculty of Science |
Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Drug
Plasmodium Prioritization Anti malarial media_common.quotation_subject Plasmodium vivax Research agenda Computational biology qv_38 wc_765 Enabling technologies Antimalarials 03 medical and health sciences qv_256 Humans media_common.cataloged_instance Medicine European Union European union 030304 developmental biology media_common 0303 health sciences CRIMALDDI biology 030306 microbiology Drug discovery business.industry Health Policy Plasmodium falciparum biology.organism_classification medicine.disease Chemical space 3. Good health Biotechnology Malaria wc_750 Infectious Diseases Commentary Parasitology business Novel targets |
Zdroj: | Malaria Journal |
ISSN: | 1475-2875 |
Popis: | The Coordination, Rationalization, and Integration of antiMALarial drug Discovery & Development Initiatives (CRIMALDDI) Consortium, funded by the EU Framework Seven Programme, has attempted, through a series of interactive and facilitated workshops, to develop priorities for research to expedite the discovery of new anti-malarials. This paper outlines the recommendations for the development of enabling technologies and the identification of novel targets. Screening systems must be robust, validated, reproducible, and represent human malaria. They also need to be cost-effective. While such systems exist to screen for activity against blood stage Plasmodium falciparum, they are lacking for other Plasmodium spp. and other stages of the parasite’s life cycle. Priority needs to be given to developing high-throughput screens that can identify activity against the liver and sexual stages. This in turn requires other enabling technologies to be developed to allow the study of these stages and to allow for the culture of liver cells and the parasite at all stages of its life cycle. As these enabling technologies become available, they will allow novel drug targets to be studied. Currently anti-malarials are mostly targeting the asexual blood stage of the parasite’s life cycle. There are many other attractive targets that need to be investigated. The liver stages and the sexual stages will become more important as malaria control moves towards malaria elimination. Sexual development is a process offering multiple targets, even though the mechanisms of differentiation are still not fully understood. However, designing a drug whose effect is not curative but would be used in asymptomatic patients is difficult given current safety thresholds. Compounds active against the liver schizont would have a prophylactic effect and Plasmodium vivax elimination requires effectors against the dormant liver hypnozoites. It may be that drugs to be used in elimination campaigns will also need to have utility in the control phase. Compounds with activity against blood stages need to be screened for activity against other stages. Natural products should also be a valuable source of new compounds. They often occupy non-Lipinski chemical space and so may reveal valuable new chemotypes. |
Databáze: | OpenAIRE |
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