| Autor: |
Batista FA; Structural Biology Unit, XB20 Drug Design, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.; Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Gyau B; Structural Biology Unit, XB20 Drug Design, Department of Pharmacy, University of Groningen, Groningen, The Netherlands., Vilacha JF; Structural Biology Unit, XB20 Drug Design, Department of Pharmacy, University of Groningen, Groningen, The Netherlands., Bosch SS; Structural Biology Unit, XB20 Drug Design, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.; Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Lunev S; Structural Biology Unit, XB20 Drug Design, Department of Pharmacy, University of Groningen, Groningen, The Netherlands., Wrenger C; Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Groves MR; Structural Biology Unit, XB20 Drug Design, Department of Pharmacy, University of Groningen, Groningen, The Netherlands. |
| Abstrakt: |
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. |
