Clemastine but not HSF1A inhibits multiple Plasmodium life stages. (A) Structures of clemastine (Clem) and a human TRiC inhibitor HSF1A. (B) Relative P. falciparum load in erythrocytes after addition of 10 μM clemastine (gray bar), 10 μM HSF1A (white bar), or DMSO (black bar) at 40 hpi (schizont). The parasite loads were measured after a 42-h incubation. (C) Relative P. berghei load in Huh7 liver cells at 48 hpi after addition of 10 μM clemastine (gray bar), 10 μM HSF1A (white bar), or DMSO (black bar) at 0 hpi. (D) Dose–response curves for clemastine inhibition of blood-stage P. falciparum when administered at the ring (R, black circles) or schizont (S, red circles) stages. Assay schematic shown above plot with R (ring), T (trophozoite), and S (schizont) developmental stages at indicated hours postinfection (hpi). Broken line indicates parasite reinvasion. (E) Dose–response curves for clemastine inhibition of liver-stage P. berghei when administered at 0 (black circles) or 24 (red circles) hpi in Huh7 cells. Assay schematic shown above plot. Data shown as the average ± SEM of three separate experiments.