In Silico Screening of Terminalia chebula Phytocompounds as Potential Inhibitors of NTCP and DDB1 in Hepatitis B Virus Infection

Year : 2026 | Volume : 13 | 01 | Page :
    By

    Pratyush Vasudha Naresh,

  1. Students, Department of Biotechnology, Ramaiah Institute of Technology, Bengaluru, Karnataka, India

Abstract

Hepatitis B virus (HBV) infection is a major global health concern, and chronic carriers are at risk of developing cirrhosis, hepatocellular carcinoma (HCC), and even death. Existing treatments can effectively inhibit viral replication, but they achieve little eradication of the virus because of covalently closed circular DNA (cccDNA) retention. In this investigation, bioactive compounds of Terminalia chebula, a plant known for its hepatoprotective and antiviral properties in traditional medicine, were screened against NTCP (7PQQ) and DDB1 (9J6K chain A), a key host protein during HBx-mediated transcription through molecular docking. In silico drug-likeness, pharmacokinetic, toxicity profiling along with binding interaction of five ligands (syringic acid, L-ascorbic acid, shikimic acid, vanillic acid and myristic acid) were examined. The Swiss ADME platform was used to predict ADME properties (Lipinski’s Rule of Five), and ProTox-II, ADMETlab 3.0 were used for toxicity predictions. Virtual screening on PyRx showed that all the ligands met Lipinski’s rules and showed high-gastrointestinal absorption. Toxicity evaluations demonstrated good safety profiles among which vanillic acid and shikimic acid were less toxic. Vanillic acid exerted the highest binding affinity to NTCP (−5.3 kcal/mol) by strong H-bonds and pi-alkyl interactions and shikimic acid revealed the best interactions with DDB1 (−6.1 kcal/mol), involving H-bonds with important residues. These findings suggest that vanillic acid and shikimic acid could be potential lead compounds for novel anti-HBV agents from Terminalia chebula.

Keywords: Hepatitis B virus, Terminalia chebula, Molecular docking, NTCP, DDB1, SwissADME, Drug-likeness, ProTox-II, ADMETlab 3.0

How to cite this article:
Pratyush Vasudha Naresh. In Silico Screening of Terminalia chebula Phytocompounds as Potential Inhibitors of NTCP and DDB1 in Hepatitis B Virus Infection. Research & Reviews: A Journal of Drug Formulation, Development and Production. 2025; 13(01):-.
How to cite this URL:
Pratyush Vasudha Naresh. In Silico Screening of Terminalia chebula Phytocompounds as Potential Inhibitors of NTCP and DDB1 in Hepatitis B Virus Infection. Research & Reviews: A Journal of Drug Formulation, Development and Production. 2025; 13(01):-. Available from: https://journals.stmjournals.com/rrjodfdp/article=2025/view=232842


References

  1. Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2022: a modelling study. Lancet Gastroenterol Hepatol. 2022;7(9):796–808.
  2. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560–1599.
  3. Lucifora J, Arzberger S, Durantel D, et al. Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection. J Hepatol. 2011;55(5):996–1003.
  4. Slagle BL, Bouchard MJ. Role of HBx in hepatitis B virus persistence and its therapeutic implications. Curr Opin Virol. 2018;30:32–38.
  5. Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife. 2012;1:e00049.
  6. Guidotti LG, Chisari FV. Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol. 2006;1:23–61.
  7. Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. J Hepatol. 2017;67(4):847–861.
  8. Revill PA, Chisari FV, Block JM, et al. A global scientific strategy to cure hepatitis B. Lancet Gastroenterol Hepatol. 2019;4(7):545–558.
  9. Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv. 2015;33(8):1582–1614.
  10. Singh R, Ahmed S, Malemnganbi P, et al. Terminalia chebula: A multipurpose tree with immense medicinal value. Pharmacogn Rev. 2021;15(29):70–76.
  11. Lee HS, Won NH, Kim KH, Lee H, Jun W, Lee KW. Antioxidant effects of aqueous extract of Terminalia chebula in vivo and in vitro. Biol Pharm Bull. 2005;28(9):1639–1644.
  12. Sharma A, Kumar S, Chashoo G, et al. Bioactive compounds and pharmacological activities of Terminalia chebula: a review. Asian J Pharm Clin Res. 2016;9(6):21–28.
  13. Kannan R, Saraswathy A, Balasubramanian R, et al. Antiviral and anti-inflammatory potential of Terminalia chebula: experimental evidence. BMC Complement Med Ther. 2020;20:145.
  14. Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, et al. IMPPAT: A curated database of Indian Medicinal Plants, Phytochemistry and Therapeutics. Sci Rep. 2018;8:4329.
  15. Kim S, Chen J, Cheng T, et al. PubChem 2023 update. Nucleic Acids Res. 2023;51(D1):D1373-D1380.
  16. Berman HM, Westbrook J, Feng Z, et al. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235-242.
  17. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717.
  18. Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018;46(W1):W257-W263.
  19. Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, Yin M, Zeng X, Wu C, Lu A, Chen X, Hou T. ADMETlab 3.0: integrating ADMET optimization for drug design. Nucleic Acids Res. 2021;49(W1):W5–W14. 
  20. Dassault Systèmes BIOVIA. Discovery Studio Visualizer v21.1.0. San Diego: Dassault Systèmes; 2021.
  21. Laskowski RA, Jabłońska J, Pravda L, Vařeková RS, Thornton JM. PDBsum: Structural summaries of PDB entries. Nucleic Acids Res. 2018;46(D1):D486-D488.
  22. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform. 2011;3:33.
  23. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461.
  24. Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015;64(12):1972–84.
  25. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1–3):3–26.
  26. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45(12):2615–23.
  27. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol. 2010;62(11):1607–21.
  28. Sanguinetti MC, Tristani-Firouzi M. hERG potassium channels and cardiac arrhythmia. Nature. 2006;440(7083):463–9.
Ahead of Print Subscription Original Research
Volume 13
01
Received 26/10/2025
Accepted 15/11/2025
Published 22/11/2025
Publication Time 27 Days
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