Computational Screening of Natural Compounds for Pemphigoid Treatment: Identification of High-Affinity Granzyme B Inhibitors

Background: Granzyme B (GzmB), a serine protease released by immune and non-immune cells, exhibits a significant presence in pemphigoid lesions. This enzymatic protein degrades extracellular matrix components, playing a crucial role in disease pathogenesis, thus presenting itself as a promising therapeutic target. This study aimed to identify compounds that can hinder GzmB by conducting computational drug discovery using the molecular docking method. Methods: To this end, 62 plant-derived compounds encompassing three distinct chemical classes (i.e., flavonoid compounds, cinnamic acid derivatives, and anthraquinones) were assessed for their binding affinities to the GzmB active site through molecular docking simulations using AutoDock 4.0. Results: The analysis revealed remarkable binding characteristics, with 50 compounds demonstrating inhibition constants at nanomolar concentrations and five compounds achieving picomolar-level inhibition. Furthermore, 21 compounds exhibited binding free energies (∆Gbinding) below -10, indicating robust interaction with the GzmB active site. Precisely, the Gibbs free energy of binding for Cynarin was calculated to be -13.13 kcal/mol. Conclusion: This study identified herbal isolates with a strong affinity for GzmB, showing potential for developing treatments for pemphigoid and other immune diseases.