Design and Computational Assessment of (1H-Pyrazolo[3,4-c] pyridin-5-yl) Sulfonamide Derivatives as Potent Hepatitis B Virus Capsid Assembly Modulators

Laoud, Aicha; Belafriekh, Abderahmane

doi:10.22036/pcr.2026.536290.2757

Design and Computational Assessment of (1H-Pyrazolo[3,4-c] pyridin-5-yl) Sulfonamide Derivatives as Potent Hepatitis B Virus Capsid Assembly Modulators

Document Type : Regular Article

Authors

Aicha Laoud ¹

Abderahmane Belafriekh ²

¹ Department of Chemical Engineering, Faculty of Chemical Engineering, University of Salah Boubnider Constantine 3, Constantine 25000, Algeria. Laboratoire d'obtention de Substances Thérapeutique – LOST. Département de Chimie, Faculté des Sciences Exactes, Université Constantine 1, 25000, Algérie

² Laboratory of LCPMM, Organic Chemistry Department, Faculty of Sciences, University of Blida 1, P. O. Box: 270 Blida, 09000, Algeria

https://doi.org/10.22036/pcr.2026.536290.2757

Abstract

Hepatitis B virus (HBV) is a significant global health concern, and the development of new antiviral agents is necessary. In this work, a comprehensive computational investigation was performed on a series of (1H-Pyrazolo[3,4-c] pyridin-5-yl) sulfonamide derivatives as potential antiviral agents to modulate HBV capsid assembly. Molecular docking studies were used to elucidate binding interactions with the HBV core protein, while atom-based 3D-QSAR modeling provided insights into key structural features governing antiviral activity. The developed 3D-QSAR model showed high statistical robustness and predictive power (R² = 0.97 for the training set, Q² = 0.80 for the test set, and RMSE = 0.17). Newly designed inhibitors, guided by contour map analysis and docking results, showed favorable binding affinity and ADME prediction, suggesting their potential as novel antiviral inhibitors.

Graphical Abstract