(A-C) Heat maps of interactions between the WLL or WLW proteasome inhibitors and distinct antimalarial agents. Assays used the Cam3.II K13WT and Cam3.II K13C580Y lines. Parasites were exposed to compounds mixed at fixed ratios of their individual IC50 values (1:0, 4:1, 2:1, 1:1, 1:2, 1:4, 0:1). (A) Asynchronous parasites were exposed for 72 hr and parasitemias were determined by flow cytometry. (B) Highly synchronized rings (0–3 hr post-invasion) or (C) trophozoites (tested 24 hr later) were exposed for 3 hr, followed by drug washouts and continued culture for 69 hr in drug-free media. Values represent the mean of the sums of the FIC50 values over the five fixed ratios of the two test compounds (excluding the 1:0 and 0:1 points). Assays were conducted on two to four independent occasions in duplicate. Data for WLW and the five top compounds (DHA, OZ439, MB, b-AP15 and ESI) are presented as isobolograms in Fig 5. ATQ, atovaquone; CQ, chloroquine; DHA, dihydroartemisinin; ESI, eeyarestatin I; LMF, lumefantrine; MB, methylene blue; PPQ, piperaquine. Means of the sums of FIC50 (mean ΣFIC50) values are reported in S12 Table.