Publication

New directions in antimalarial target validation

Batista, F. A., Gyau, B., Vilacha, J. F., Bosch, S. S., Lunev, S., Wrenger, C. & Groves, M. R., 1-Feb-2020, In : Expert Opinion on Drug Discovery. 15, 2, p. 189-202 14 p.

Research output: Contribution to journalReview articleAcademicpeer-review

Introduction: Malaria is one of the most prevalent human infections worldwide with over 40% of the world's population living in malaria-endemic areas. In the absence of an effective vaccine, emergence of drug-resistant strains requires urgent drug development. Current methods applied to drug target validation, a crucial step in drug discovery, possess limitations in malaria. These constraints require the development of techniques capable of simplifying the validation of Plasmodial targets. Areas covered: The authors review the current state of the art in techniques used to validate drug targets in malaria, including our contribution - the protein interference assay (PIA) - as an additional tool in rapid in vivo target validation. Expert opinion: Each technique in this review has advantages and disadvantages, implying that future validation efforts should not focus on a single approach, but integrate multiple approaches. PIA is a significant addition to the current toolset of antimalarial validation. Validation of aspartate metabolism as a druggable pathway provided proof of concept of how oligomeric interfaces can be exploited to control specific activity in vivo. PIA has the potential to be applied not only to other enzymes/pathways of the malaria parasite but could, in principle, be extrapolated to other infectious diseases.

Original languageEnglish
Pages (from-to)189-202
Number of pages14
JournalExpert Opinion on Drug Discovery
Volume15
Issue number2
Early online date20-Jan-2020
Publication statusPublished - 1-Feb-2020

    Keywords

  • Protein oligomerisation, malaria, drug target validation, phenotypic mapping, FALCIPARUM DIHYDROOROTATE DEHYDROGENASE, PLASMODIUM-VIVAX DHFR, MALARIA PARASITES, DRUG TARGET, PIPERAQUINE RESISTANCE, TRANSGENE EXPRESSION, NEGATIVE SELECTION, LEAD OPTIMIZATION, GENE-EXPRESSION, BLOOD STAGES

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