Unveiling the Inhibitory Potential of Nigella sativa Phytochemicals Against TG2: Computational and ADMET Approaches for Celiac Disease

Weam Alyoubi, Hani Mohammed Ali, Ahmad Firoz

Abstract


Background: Celiac disease (CD) is an autoimmune condition initiated by the ingestion of gluten in individuals with a genetic susceptibility. Transglutaminase 2 (TG2) plays a central role in CD pathogenesis by deamidating gluten peptides, enhancing their immunogenicity. This study explores the inhibitory potential of Nigella sativa-derived phytochemicals against TG2.

Methods: A library of 132 Nigella sativa-derived phytochemicals was screened using molecular docking to identify candidates with high binding affinities for TG2. The top four compounds were further evaluated for pharmacokinetic properties (ADME) and toxicity using SwissADME, admetSAR, pkCSM, and ProTox-II. Molecular dynamics (MD) simulations (100 ns) were conducted to assess the stability of protein-ligand complexes based on RMSD, RMSF, hydrogen bonding, radius of gyration (Rg), and solvent-accessible surface area (SASA).

Results: Docking analysis identified four phytochemicals with strong binding affinities to the TG2 active site. ADME and toxicity profiling confirmed favorable drug-like properties and acceptable safety profiles. MD simulations demonstrated stable interactions between TG2 and three of the selected compounds, with consistent binding stability and minimal structural deviations observed throughout the simulations.

Conclusion: Three Nigella sativa phytochemicals exhibit promising characteristics as potential TG2 inhibitors. These findings provide a computational basis for further experimental validation and development of novel therapies for celiac disease.

Keywords: Celiac Disease, Molecular Docking, ADME, Molecular Dynamics Simulation, Nigella sativa, TG2


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DOI: https://doi.org/10.62940/als.v13i2.3805

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