Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36 Plasmodium falciparum targets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE). They were further evaluated in Molecular dynamics (MD). Twenty-five protein–ligand complexes were finally retained from the 28,656 (36 × 796) dockings. Hit GRIM scores (0.58 to 0.78) showed their molecular interaction similarity to co-crystallized ligands. Minimum LipE (3), SEI (23) and BEI (7) were in at least acceptable thresholds for hits. Binding energies ranged from −6 to −11 kcal/mol. Ligands showed stability in MD simulation with good hydrogen bonding and favorable protein–ligand interactions energy (the poorest being −140.12 kcal/mol). In vitro testing showed 4 active compounds with two having IC 50 values in the single-digit μM range.
【저자키워드】 Virtual screening, High-throughput screening, Drug discovery and development, 【초록키워드】 molecular dynamics, antimalarial, MD simulation, stability, target, DrugBank, threshold, Ligand, Interaction, similarity, Efficiency, Plasmodium falciparum, ligands, Compound, minimum, molecular interaction, matching, binding efficiency, approach, benefit, selected, evaluated, screened, complexes, retained, ranged, co-crystallized, GRIM, 【제목키워드】 in vitro, FDA, proteome, Compound, Computational drug, approved, Potential,