Abstract
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Highlights
Several whole-parasite chemical library screens have identified thousands of compounds with potent antimalarial activity (Guiguemde et al, 2010; Kato et al, 2016)
Sequence similarity between Human NPC1 (hNPC1) and Plasmodium falciparum NCR1 (PfNCR1) is restricted to portions of the transmembrane region and to approximately 45 amino acids N-terminal to the sensing domain (SSD)
Inclusion of the C-terminal green-fluorescent protein (GFP) did not alter the sensitivity to MMV009108 (Figure 1D), while parasites with single mutations in PfNCR1 were resistant to the compounds with which they were selected (Figure 1D–F, Figure 1—source data 2)
Summary
Several whole-parasite chemical library screens have identified thousands of compounds with potent antimalarial activity (Guiguemde et al, 2010; Kato et al, 2016). It is important to identify targets of these compounds. Target identification can be extremely challenging, especially in organisms like Plasmodium that contain large numbers of proteins with unknown. Evolution of compound-resistant malaria parasites can be helpful in the discovery of the molecular mechanisms by which compounds kill the organism (Rathod et al, 1994; Rottmann et al, 2010; Vaidya et al, 2014; Istvan et al, 2017)
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