Mohebbi, A.; Naderi, M.; Sharifian, K.; Behnezhad, F.; Mohebbi, M.; Gholami, A.; Askari, F.S.; Mirarab, A.; Monavari, S.H. Computational-Aided Reproposing Drug(s) and Discovery for Potential Antivirals Targeting Hepatitis B Virus Capsid Protein. Preprints2023, 2023100425. https://doi.org/10.20944/preprints202310.0425.v1
APA Style
Mohebbi, A., Naderi, M., Sharifian, K., Behnezhad, F., Mohebbi, M., Gholami, A., Askari, F.S., Mirarab, A., & Monavari, S.H. (2023). Computational-Aided Reproposing Drug(s) and Discovery for Potential Antivirals Targeting Hepatitis B Virus Capsid Protein. Preprints. https://doi.org/10.20944/preprints202310.0425.v1
Chicago/Turabian Style
Mohebbi, A., Azam Mirarab and Seyed Hamidreza Monavari. 2023 "Computational-Aided Reproposing Drug(s) and Discovery for Potential Antivirals Targeting Hepatitis B Virus Capsid Protein" Preprints. https://doi.org/10.20944/preprints202310.0425.v1
Abstract
Background: Chronic Hepatitis B Virus (HBV) infection is a global health concern, associated with severe liver diseases, necessitating ongoing research on novel drug candidates. This study aims to identify potential drug candidates targeting HBV core protein (HBcAg) and disrupting capsid assembly, a critical step in the virus's life cycle. Methods: HBcAg in complex with HBV inhibitors were obtained from the Protein Data Bank (PDB). CavityPlus server was used for analysis of druggable cavity. Structure-based pharmacophores were extracted from identified cavities, and potential allosteric ligand binding sites were assessed using CavPharmer, CorrSite, and CovCys. LigandScout was employed for ligand-based pharmacophore screening against an FDA-approved library. The ZINC database was screened with features extracted from CavPharmer. Molecular docking studies were conducted using Autodock Vina. Lead compounds were selected based on docking scores, binding modes, and interactions within the druggable cavity. Results: Strong druggable pockets were found for Ciclopirox, while Compound 24, NVR10-001E2, and others showed medium to weak pockets. Ligand-based pharmacophores varied in size and complexity. Screening revealed potential hits matching these pharmacophores, including Ciclopirox olamine, Voriconazole, Enasidenib, and Statins. A large compound database search yielded additional hits like ZINC86859997 and ZINC63280172. Docking analyses confirmed these hits' potential, highlighting their interactions with critical HBc protein residues, offering promising leads for hepatitis B drug development. Conclusions: Voriconazole, Enasidenib, and Lovastatin have shown promises. These hits displayed favorable interactions with crucial HBc protein residues, indicating their potential as lead compounds The mechanism of action of statins with anti-HBV activities also highlighted. This comprehensive approach offers valuable insights into targeting HBc protein for antiviral drug discovery.
Keywords
hepatitis B; antiviral; drug discovery; HBc protein; pharmacophore-based screening; drug repurposing
Subject
Biology and Life Sciences, Virology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
