Fig. 1

Overview of the antimalarial target discovery and drug discovery processes. Phenotypic screening is undertaken with diverse compound libraries using assays that target different stages of the malaria life cycle: blood stage, liver stage, and gametocytes. Compounds that demonstrate potent antimalarial activity can go directly into hit-to-lead studies and can progress to clinical studies. Simultaneously, target discovery can be carried out using different methods, such as affinity chromatography, in vitro evolution and whole-genome analysis (IVIEWGA) [17], and metabolic profiling. Target validation can be carried out using gene knockdown approaches such as the TetR-aptamer system [18]. Genome-wide essentiality data can also help with target validation. Target structures can then be determined, and recombinant protein targets can be used in biochemical screens. Hit-to-lead optimization can occur without knowing a target, although development is facilitated when the target is known