Exploring the HNE-inhibitory potential of in silico selected Moringa oleifera defense proteins

Human neutrophil elastase (HNE) is a primary therapeutic target for the treatment of severe inflammatory disorders. This study explores the HNE-inhibitory potential of peptides derived from Moringa oleifera 2S albumin and chitin-binding proteins, leveraging the inherent proteolytic stability of these defense-related scaffolds. Using a pipeline-assisted approach, mass spectrometry-based proteomics was combined with in silico proteolysis and molecular docking to guide the investigation. Enzyme kinetic studies established a competitive mode of inhibition, confirming the predicted binding mechanism. Initial virtual screenings utilized porcine pancreatic elastase as a structural surrogate, followed by rigorous docking simulations against the HNE catalytic site to evaluate clinical applicability. Molecular docking identified key residues at the protein–ligand interface that are likely responsible for stabilizing the complex across multiple subsites of the HNE pocket. Assays with chemically synthesized lead peptides corroborated the computational predictions, demonstrating notable HNE-inhibitory activity. These findings present an integrated computational-experimental workflow for the rapid identification of plant-derived inhibitors and offer promising, stable lead scaffolds for the development of scalable, next-generation anti-inflammatory agents.

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