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<p>Malaria remains a major health challenge, intensified by the spread of drug-resistant strains. To address this, we explored natural products and derivatives for antimalarial potential using <i>in silico</i> approaches. Through a similarity-based optimization strategy, molecular docking (Vina) and deep learning-based screening (Gnina) identified <b>CE-326597</b> as a strong binder of <i>Plasmodium falciparum</i> enoyl-ACP reductase. Molecular dynamics simulations with a self-assembly setup showed spontaneous binding, with the ligand approaching the target from bulk solvent within 15 ns and maintaining stable interactions throughout 200 ns. Network pharmacology revealed that <b>CE-326597</b> disrupts key parasite pathways (SRC, EGFR, ESR1) and modulates host receptors (HTR1A, HTR7, DRD4) linked to immune regulation. With a favorable safety profile from Phase 1 clinical trials for obesity, <b>CE-326597</b> emerges as a promising repurposing candidate for malaria. Further <i>in vitro</i> and <i>in vivo</i> studies are warranted to confirm its therapeutic potential.</p>

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Network pharmacology, molecular docking and molecular dynamics simulation suggest CE-326597 as an antimalarial molecule

  • 期刊论文

  • 发表日期：

    2025年12月10日

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  • Daniel M. Shadrack,
  • Angelina Makaye,
  • Andima Moses,
  • Hulda S. Swai

摘要

Malaria remains a major health challenge, intensified by the spread of drug-resistant strains. To address this, we explored natural products and derivatives for antimalarial potential using in silico approaches. Through a similarity-based optimization strategy, molecular docking (Vina) and deep learning-based screening (Gnina) identified CE-326597 as a strong binder of Plasmodium falciparum enoyl-ACP reductase. Molecular dynamics simulations with a self-assembly setup showed spontaneous binding, with the ligand approaching the target from bulk solvent within 15 ns and maintaining stable interactions throughout 200 ns. Network pharmacology revealed that CE-326597 disrupts key parasite pathways (SRC, EGFR, ESR1) and modulates host receptors (HTR1A, HTR7, DRD4) linked to immune regulation. With a favorable safety profile from Phase 1 clinical trials for obesity, CE-326597 emerges as a promising repurposing candidate for malaria. Further in vitro and in vivo studies are warranted to confirm its therapeutic potential.