Fig 2.

Activity of MMV1557817 against P. falciparum and ex vivo P. vivax. (A) Killing action of MMV1557817 determined by a standard 72 h ring killing assay. Plotted is the mean ± standard error of the mean (n = 3 performed in triplicate). (B) Representative Giemsa-stained Pf3D7 parasites treated with MMV1557817 over two cycles (C1, cycle 1; C2, cycle 2) beginning at 4 h post-infection with 5× or 10× the EC₅₀ or DMSO at the concentration present in the 10× EC₅₀ treatment. Treated parasites did not progress past ring stage. (C) Assessment of MMV1557817 activity on ring- and trophozoite-stage Pf3D7. Parasites were incubated in 10× EC₅₀ MMV1557817 for either 24 or 48 h before the compound was washed off and parasites were allowed to grow for a further 48 h. Survival was determined via Sybr Green I assay and compared with vehicle (DMSO)-treated controls. Shown is the mean ± standard deviation (n = 4). Statistical significance was determined using a one-way ANOVA. (D) Pf3D7 viability time course profiles for MMV1557817 compared with chloroquine. The lag phase is indicated on the graph and summarized in the table below, along with the log of the parasite reduction ratio (PRR) and the 99.9% parasite clearance time (PCT; n ≥ 2 performed in quadruple). (E) Killing action of MMV1557817 and current antimalarial compounds against ex vivo P. falciparum (solid icons) and P. vivax (clear icons) obtained from clinical isolates. No significant differences in EC₅₀ values were observed for these compounds between species, with the exception of chloroquine.