IN SILICO NETWORK PHARMACOLOGY AND MOLECULAR DOCKING ANALYSIS OF APIGENIN FROM DRACUNCULUS VULGARIS SCHOTT. AS AN IMMUNOMODULATORY ADJUNCT AGAINST CANDIDA AURIS PNEUMONIA INFECTION

Sachin Bhusari*, Rukayya Shaikh, Pravin Wakte

This computational polypharmacology paradigm interrogates the pleiotropic immunomodulatory efficacy of Dracunculus vulgaris Schott. (Araceae)—a flavonoid-replete Mediterranean geophyte—and its eponymous flavone, apigenin (4',5,7-trihydroxyflavone), as an adjuvant against Candida auris-induced pneumonitis, an iatrogenic, pan-echinocandin-recalcitrant mycosis in immunosenescent cohorts. Leveraging an ensemble of bioinformatic repositories (GeneCards, DrugBank, STRING [PPI fidelity >0.7], Cytoscape [CytoHubba topological analytics]), we delineated a holistic targetome from 110 C. auris pneumonitis-linked loci. Topological pruning—via degree centrality thresholding and KEGG hyperenrichment (e.g., hsa04664 FcγR transduction, hsa04060 cytokinome)—distilled 10 nexus genes, underscoring entelechy in Fc-mediated efferocytosis and IL-20/IL-10 paracrine rheostats, evincing apigenin's epistatic orchestration of antifungal allostasis. Iterative PPI cartography unveiled modular confluences: PTPRC (CD45 tyrosine phosphatase, nodal degree=48) galvanizing adaptin dephosphorylation, FCGR3B/FCGR3A (affinity-tuned IgG opsonophagocytes, degrees=42/39) amplifying ADCC cascades, and IL10 (suppressor cytokine, degree=35) interfacing with TNFRSF/FASLG (apoptogenic effectors) for dichotomous pro-resolvin homeostasis. AutoDock Vina docking (exhaustiveness=8) evinced apigenin's enthalpic supremacy (ΔG=−8.5 to −9.2 kcal/mol) over caspofungin (−6.2 to −7.1 kcal/mol). In SpCas9-PTPRC (PDB:7QR8), apigenin evinced Ser1082 H-bonding (2.6 Å) and Leu1050 π-alkyl occlusion (4.0 Å); FCGR3B (PDB:6EAQ) featured Asn129/Gln131 polar clamps (2.4–2.7 Å), potentiating glycohyaluronan-mediated hyphal lysis. Corroborants encompassed FcγRIIIa (PDB:3AY4; Ser141, 2.5 Å) and IL-20RA/IL20RB heteromer (PDB:4DOH; Glu48/Arg52, 2.6–2.9 Å), ratifying pan-nodal allostery. Post-Venn radial/clustered holography fused IL10 antilog loops with PTPRC phosphatidic flux and FCGR efferent volleys. Empirical consilience: apigenin (20–80 μM) escalates alveolar macrophage efferocytosis, cytokinomic equipoise, and ROS/NETotic rheology in candidal pneumonitides. Venn intersect (204 pneumonitides vs. 110 apigenin loci) nominated PTPRC/FCGR3B as eudaimonic fulcra, with IL10-FASLG dihedrals arbitrating inflammasomopathy. Apigenin's ΔΔG hegemony and interactomic depth nominate it as a non-nephrotoxic echinocandin synerget, imperating ex vivo/in vivo attrition for mycoarmamentarium augmentation.