Targeting β-1,4-endoglucanase of the root-knot nematode Meloidogyne incognita with plant-derived polyphenols: an in-silico screening approach

Root-knot nematodes, especially Meloidogyne incognita, inflict significant yield reductions in horticultural and crop plants, and the excessive dependence on synthetic nematicides has prompted apprehensions about resistance, environmental longevity, and non-target toxicity. This study sought to identify plant-derived polyphenolic scaffolds with anticipated inhibitory capacity against β-1,4-endoglucanase from M. incognita, a crucial effector in cell wall degradation that facilitates host penetration and feeding-site establishment. A panel of ten dietary and medicinal polyphenols (quercetin, kaempferol, myricetin, luteolin, apigenin, naringenin, catechin, rutin, genistein, and baicalein) was assembled and evaluated in silico utilizing SwissADME and pkCSM to determine drug-likeness, pharmacokinetics, and toxicity, subsequently followed by molecular docking into the PrankWeb-predicted active site of a three-dimensional model of β-1,4-endoglucanase. The highest-ranked complexes underwent additional assessment by 100 ns explicit-solvent molecular dynamics simulations utilizing GROMACS and MM-GBSA binding free-energy computations. All polyphenols exhibited moderate predicted affinity (docking scores ranging from approximately -6.1 to -7.3 kcal·mol⁻¹), with baicalein and myricetin establishing extensive hydrogen-bond and aromatic stacking networks within the catalytic groove, demonstrating greater stability in backbone and active-site dynamics compared to the apo enzyme in molecular dynamics trajectories. MM-GBSA research found a more favorable total binding free energy for baicalein compared to myricetin, mostly influenced by van der Waals and electrostatic interactions, but ADMET predictions revealed low systemic toxicity and restricted central nervous system penetration for both ligands. In the context of a predicted-structure-based and entirely computational study, baicalein emerges as the top-ranked predicted binder, with myricetin serving as a secondary candidate for subsequent experimental assessment, rather than as confirmed inhibitors of β-1,4-endoglucanase in M. incognita .