In silico Identification of Potential Hepatitis B Virus HBx Inhibitors Through Molecular Docking Analysis
DOI:
https://doi.org/10.71204/qbf0ba53Keywords:
Hepatitis, Bioinformatics, HBV, HBx, Computational Drug DesignAbstract
Hepatitis B virus (HBV) remains a major contributor to chronic liver disease worldwide and represents a significant global health challenge. The HBx protein plays an important role in HBV replication and viral pathogenesis and is therefore considered a promising therapeutic target. In the present study, an in silico molecular docking approach was employed to identify potential HBx inhibitors from a selected group of fourteen compounds. The three-dimensional structure of the HBx protein was predicted using the I-TASSER server, and the selected compounds were subjected to molecular docking using PyRx and AutoDock Vina. The docking results revealed that several compounds exhibited favorable predicted binding affinities toward HBx, with SC75741 showing the most favorable docking score (−9.8 kcal/mol), followed by Rutin (−9.1 kcal/mol), Cynarin (−8.6 kcal/mol), and Ledipasvir (−8.4 kcal/mol). Notably, Cynarin, which is not currently an approved anti-HBV drug, demonstrated a favorable docking score and interactions with several important HBx residues, highlighting its potential as a candidate lead compound for further investigation. Overall, the findings suggest that the identified compounds, particularly SC75741, Rutin, Cynarin, and Ledipasvir, may serve as potential candidates for HBx-targeted anti-HBV drug discovery.
References
Ahmadi, N., Aghasadeghi, M., Hamidi-Fard, M., Motevalli, F., & Bahramali, G. (2024). Reverse vaccinology and immunoinformatic approach for designing a bivalent vaccine candidate against hepatitis A and hepatitis B viruses. Molecular Biotechnology, 66(9), 2362–2380. https://doi.org/10.1007/s12033-023-00867-z
Baei, B., Askari, P., Askari, F. S., Kiani, S. J., & Mohebbi, A. (2025). Pharmacophore modeling and QSAR analysis of anti-HBV flavonols. PLOS ONE, 20(1), Article e0316765. https://doi.org/10.1371/journal.pone.0316765
Baroroh, U., Muscifa, Z. S., Destiarani, W., Rohmatullah, F. G., & Yusuf, M. (2023). Molecular interaction analysis and visualization of protein-ligand docking using Biovia Discovery Studio Visualizer. Indonesian Journal of Computational Biology, 2(1), 22–30. https://doi.org/10.24198/ijcb.v2i1.46322
Che, X., Liu, Q., & Zhang, L. (2023). An accurate and universal protein-small molecule batch docking solution using AutoDock Vina. Results in Engineering, 19, Article 101335. https://doi.org/10.1016/j.rineng.2023.101335
Dallakyan, S., & Olson, A. J. (2015). Small-molecule library screening by docking with PyRx. In J. E. Hempel, C. H. Williams, & C. C. Hong (Eds.), Chemical biology: Methods and protocols (Methods in Molecular Biology, Vol. 1263, pp. 243–250). Springer. https://doi.org/10.1007/978-1-4939-2269-7_19
Gholizadeh, O., Akbarzadeh, S., Ghazanfari Hashemi, M., Gholami, M., Amini, P., Yekanipour, Z., Tabatabaie, R., Yasamineh, S., Hosseini, P., & Poortahmasebi, V. (2023). Hepatitis A: Viral structure, classification, life cycle, clinical symptoms, diagnosis error, and vaccination. Canadian Journal of Infectious Diseases and Medical Microbiology, 2023, Article 4263309. https://doi.org/10.1155/2023/4263309
Hamadalnil, Y., & Altayb, H. N. (2024). In silico molecular study of hepatitis B virus X protein as a therapeutic target. Journal of Biomolecular Structure and Dynamics, 42(8), 4002–4015. https://doi.org/10.1080/07391102.2023.2217920
Hu, J., Protzer, U., & Siddiqui, A. (2019). Revisiting hepatitis B virus: Challenges of curative therapies. Journal of Virology, 93(20), Article e01032-19. https://doi.org/10.1128/JVI.01032-19
Kanwal, S., Jamil, F., Ali, A., & Sehgal, S. A. (2017). Comparative modeling, molecular docking, and revealing of potential binding pockets of RASSF2; a candidate cancer gene. Interdisciplinary Sciences: Computational Life Sciences, 9(2), 214–223. https://doi.org/10.1007/s12539-016-0145-z
Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., & Bolton, E. E. (2023). PubChem 2023 update. Nucleic Acids Research, 51(D1), D1373–D1380. https://doi.org/10.1093/nar/gkac956
Ko, C., Chakraborty, A., Chou, W.-M., Hasreiter, J., Wettengel, J. M., Stadler, D., Bester, R., Asen, T., Zhang, K., Wisskirchen, K., McKeating, J. A., Ryu, W.-S., & Protzer, U. (2018). Hepatitis B virus genome recycling and de novo secondary infection events maintain stable cccDNA levels. Journal of Hepatology, 69(6), 1231–1241. https://doi.org/10.1016/j.jhep.2018.08.012
Martyn, E., Eisen, S., Longley, N., Harris, P., Surey, J., Norman, J., Brown, M., Sultan, B., Maponga, T. G., Iwuji, C., Flanagan, S., Ghosh, I., Story, A., & Matthews, P. C. (2023). The forgotten people: Hepatitis B virus (HBV) infection as a priority for the inclusion health agenda. eLife, 12, Article e81070. https://doi.org/10.7554/eLife.81070
Mohebbi, A., Ghorbanzadeh, T., Naderifar, S., Khalaj, F., Askari, F. S., & Sammak, A. S. (2023). A fragment-based drug discovery developed on ciclopirox for inhibition of hepatitis B virus core protein: An in silico study. PLOS ONE, 18(5), Article e0285941. https://doi.org/10.1371/journal.pone.0285941
Naderi, M., Hosseini, S. M., Besharat, S., Behnampour, N., Shahramian, I., & Moradi, A. (2023). Clinical and virological aspects of core and pre-core mutations in three generations of chronic hepatitis B virus patients. Future Virology, 18(6), 349–358. https://doi.org/10.2217/fvl-2022-0216
Parvez, M. K., Rehman, M. T., Alam, P., Al-Dosari, M. S., Alqasoumi, S. I., & Alajmi, M. F. (2019). Plant-derived antiviral drugs as novel hepatitis B virus inhibitors: Cell culture and molecular docking study. Saudi Pharmaceutical Journal, 27(3), 389–400. https://doi.org/10.1016/j.jsps.2018.12.008
Pathak, R. K., Baunthiyal, M., Taj, G., & Kumar, A. (2014). Virtual screening of natural inhibitors to the predicted HBx protein structure of hepatitis B virus using molecular docking for identification of potential lead molecules for liver cancer. Bioinformation, 10(7), 428–435. https://doi.org/10.6026/97320630010428
Patil, V. S., Harish, D. R., Charla, R., Bhandare, V. V., Gujarathi, S. S., Beerwala, F. A., Patil, P. P., Jalalpure, S. S., Hegde, H. V., & Roy, S. (2025). Flavonoids of Andrographis paniculata regulate hepatitis B virus replication and hepatocellular carcinoma progression: Evidence from computational and experimental studies. BMC Complementary Medicine and Therapies, 25(1), Article 95. https://doi.org/10.1186/s12906-025-04807-z
Rasool, M., Malik, A., Waquar, S., Tul-Ain, Q., Jafar, T. H., Rasool, R., Kalsoom, A., Ghafoor, M. A., Sehgal, S. A., Gauthaman, K., Naseer, M. I., Al-Qahtani, M. H., & Pushparaj, P. N. (2018). In-silico characterization and in-vivo validation of albiziasaponin-A, iso-orientin, and salvadorin using a rat model of Alzheimer’s disease. Frontiers in Pharmacology, 9, Article 730. https://doi.org/10.3389/fphar.2018.00730
Rizzo, G. E. M., Cabibbo, G., & Craxì, A. (2022). Hepatitis B virus-associated hepatocellular carcinoma. Viruses, 14(5), Article 986. https://doi.org/10.3390/v14050986
Saeed, U., Piracha, Z. Z., Alrokayan, S., Hussain, T., Almajhdi, F. N., & Waheed, Y. (2023). Immunoinformatics and evaluation of peptide vaccines derived from global hepatitis B viral HBx and HBc proteins critical for covalently closed circular DNA integrity. Microorganisms, 11(12), Article 2826. https://doi.org/10.3390/microorganisms11122826
Schoch, C. L., Ciufo, S., Domrachev, M., Hotton, C. L., Kannan, S., Khovanskaya, R., Leipe, D., McVeigh, R., O’Neill, K., Robbertse, B., Sharma, S., Soussov, V., Sullivan, J. P., Sun, L., Turner, S., & Karsch-Mizrachi, I. (2020). NCBI Taxonomy: A comprehensive update on curation, resources and tools. Database, 2020, Article baaa062. https://doi.org/10.1093/database/baaa062
Shaikh, I. A., Muddapur, U. M., C, K., Badiger, S., Kulkarni, M., Mahnashi, M. H., Alshamrani, S. A., Huneif, M. A., More, S. S., Khan, A. A., & Iqubal, S. M. S. (2022). In silico molecular docking and simulation studies of protein HBx involved in the pathogenesis of hepatitis B virus-HBV. Molecules, 27(5), Article 1513. https://doi.org/10.3390/molecules27051513
Tsukuda, S., & Watashi, K. (2020). Hepatitis B virus biology and life cycle. Antiviral Research, 182, Article 104925. https://doi.org/10.1016/j.antiviral.2020.104925
Tufon, K. A., Meriki, H. D., Kwenti, T. E., Tony, N. J., Malika, E., Bolimo, A. F., Kouanou, Y. S., Nkuo-Akenji, T., & Anong, D. N. (2019). HBV transmission risk assessment in healthcare workers, household and sexual contacts of HBV infected patients in the Southwest Region of Cameroon. Oman Medical Journal, 34(4), 313–321. https://doi.org/10.5001/omj.2019.62
Ugbaja, S. C., Mushebenge, A. G.-A., Kumalo, H., Ngcobo, M., & Gqaleni, N. (2025). Potential benefits of in silico methods: A promising alternative in natural compound’s drug discovery and repurposing for HBV therapy. Pharmaceuticals, 18(3), Article 419. https://doi.org/10.3390/ph18030419
UniProt Consortium (2021). UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Research, 49(D1), D480–D489. https://doi.org/10.1093/nar/gkaa1100
Velkov, S., Ott, J. J., Protzer, U., & Michler, T. (2018). The global hepatitis B virus genotype distribution approximated from available genotyping data. Genes, 9(10), Article 495. https://doi.org/10.3390/genes9100495
Yang, J., Yan, R., Roy, A., Xu, D., Poisson, J., & Zhang, Y. (2015). The I-TASSER Suite: Protein structure and function prediction. Nature Methods, 12(1), 7–8. https://doi.org/10.1038/nmeth.3213
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Maryam Aliza, Bibi Haleema (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles published in this journal are licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are properly credited. Authors retain copyright of their work, and readers are free to copy, share, adapt, and build upon the material for any purpose, including commercial use, as long as appropriate attribution is given.
How to Cite
