Repurposing Biomolecules from Aerva javanica Against DDX3X in LAML: A Computer-Aided Therapeutic Approach

Acute Myeloid Leukemia (LAML) is a life-threatening hematological malignancy, and the DEAD-box helicase 3 X-linked (<i>DDX3X</i>) gene is a potential yet underexplored target gene for LAML. Biomolecules derived from medicinal plants like <i>Aerva javanica</i> offer a great source of therapeutic candidates. This study aimed to investigate the role of <i>DDX3X</i> in LAML and identify plant-derived biomolecules that could inhibit <i>DDX3X</i> using computational approaches. Pan-cancer mutational profiling, a transcriptomic analysis, survival, protein-protein interaction networks, and a principal component analysis (PCA) were employed to elucidate functional associations and transcriptomic divergence. Subsequently, biomolecules from <i>A. javanica</i> were subjected to in silico screening using molecular docking and ADMET profiling. The docking protocol was validated using RK-33, a known <i>DDX3X</i> inhibitor. <i>DDX3X</i> was found to be linked to key leukemogenic pathways, including Wnt/β-catenin and MAPK signaling, indicating it to be a potential target. Molecular docking of <i>A. javanica</i> compounds revealed CIDs 15559724, 5490003, and 74819331 as potent <i>DDX3X</i> inhibitors with strong binding affinity and favorable pharmacokinetic and toxicity profiles compared to RK-33. This study highlights the importance of <i>DDX3X</i> in LAML pathogenesis and suggests targeting it using plant-derived inhibitors, which may require further in vitro and in vivo validation.