Fig. 2: PfeEF2 mutations mediating varying levels of cabamiquine resistance across infection models.
From: Propensity of selecting mutant parasites for the antimalarial drug cabamiquine
a Venn diagram of PfeEF2 amino acids and their locations subject to mutations under cabamiquine exposure in vitro, in NSG mouse, and in P. falciparum VIS. b Table with biomarkers of mutants selected in vitro in MIR studies (3D7, 7G8, and Dd2)7, in culture-adapted field isolates, in P. falciparum-infected NSG mice (3D7)9, or in P. falciparum VIS (3D7)10. Wild-type EC50 values were 0.28 nM (3D7), 0.47 nM (Pf3D70087/N9 in serum), 0.24 nM (7G8), 0.19 nM (Dd2), 0.57 nM (3D7_MM), 0.46 nM (3D7_FS), 0.64 nM (EEF192), and 0.41 nM (EEF209). Low: EC50 = 1–10 nM (blue); Medium: EC50 > 10–100 nM (orange); High: EC50 > 100 nM (red). *EC50 not determined; ** field isolates (Mali, 2021); *** obtained from a free concentration ratio of the human Cav0–24h (corrected for human plasma protein binding of 83%) and P. falciparum 3D7 EC50 (corrected for Albumax binding of 45.3%); **** obtained from a free concentration ratio of the Cav0–24h (249 nM) in NSG mice treated with a single dose of cabamiquine at 12 mg/kg (p.o.) and P. falciparum 3D7 EC50. § Mixed population. MIR minimum inoculum for resistance, VIS volunteer infection studies, NSG NOD/SCID/IL2rγnull, ND not defined, WT wild type.
