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Submitted: 23 Feb 2025
Revision: 25 May 2025
Accepted: 27 May 2025
ePublished: 14 Sep 2025
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Avicenna J Dent Res. Inpress.
doi: 10.34172/ajdr.2271

Original Article

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

Nrgar Sharifinejad ORCID logo, Yasamin Barakian* ORCID logo, Amir Taherkhani* ORCID logo, Tina Mazaheri ORCID logo
*Corresponding Authors: Email: dr.ybarakian@muq.ac.ir; Email: amir.007.taherkhani@gmail.com

Abstract

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. Methods: This study evaluated 62 plant-derived compounds encompassing three distinct chemical classes: Flavonoid compounds, Cinnamic acid derivatives, and Anthraquinones. These compounds 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.
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