Article Sidebar

Submitted
Jan 17, 2023
Published
May 18, 2023
Download
Pdf
Statistic
Read Counter : 356 Download : 276

Downloads

Download data is not yet available.

Main Article Content

Abstract

Naringin is a secondary metabolite compound of the flavonoid group which is generally found in plants that are consumed and traditionally used as medicine. The aim of this study was to examine the potential of naringin as a candidate for hepatitis B virus replication inhibitor using an in-silico approach. This research uses exploratory descriptive method with molecular docking analysis was carried out using the blind docking technique. The 3D structures of naringin and reference ligands were collected from the PubChem database, and the 3D structures of target proteins were collected from the PDB database. The target protein used is the hepatitis B virus capsid protein with PDB ID: 5GMZ. Docking analysis was performed using AutoDock Vina which is integrated into PyRx. Docking results were visualized using the PyMol software and Biovia Discovery Studio 2019. The results of the analysis showed that the binding affinity of all simulation models between naringin and the HBV capsid protein ranged from -7.1 to -7.9 kcal/mol. The binding site formed between naringin and the receptor corresponds to the reference ligand, involving the same 12 amino acid residues, namely PHE 23, PRO 25, LEU 30, THR 33, TRP 102, ILE 105, SER 106, PHE 110, TYR 118, ILE 139, LEU 140, and SER 141. Based on these results, it can be concluded that the naringin compound has the same bioactivity as the reference ligand in inhibiting viral replication, so that naringin has the potential as a candidate for hepatitis B virus replication inhibitor

Keywords

Antivirus Hepatitis Molecular docking Naringin Natural compounds

Article Details

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Author Biographies

Muhammad Khalil, Universitas Samudra

Department of Biology Education, Faculty of Teacher Training, Universitas Samudra.
Jl. Prof. Syarief Thayeb, Langsa, 24416, Aceh, Indonesia

Muh. Nur Akbar, Universitas Negeri Gorontalo

Department of Biology Education, Faculty of Mathematics and Natural Science, Universitas Negeri Gorontalo.
Jl. Jendral Sudirman 6, Gorontalo, 96128, Gorontalo  

Ardiyas Robi Saputra, Universitas Negeri Malang

Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang.
Jl. Semarang 5, Malang, 65145, East Java, Indonesia

Subhan Hadi Kusuma, Osaka University

Graduate School of Frontier Biosciences, Osaka University
1-3 Yamadaoka, Sulta, 565-0871, Osaka, Japan

 

References

  1. Ahmad Khan, M. S., & Ahmad, I. (2019). Herbal medicine: current trends and future prospects. In New Look to Phytomedicine (pp. 3–13). https://doi.org/10.1016/B978-0-12-814619-4.00001-X
  2. Atkovska, K., Samsonov, S., Paszkowski-Rogacz, M., & Pisabarro, M. (2014). Multipose Binding in Molecular Docking. International Journal of Molecular Sciences, 15(2), 2622–2645. https://doi.org/10.3390/ijms15022622
  3. Bitencourt-Ferreira, G., Pintro, V. O., & de Azevedo, W. F. (2019). Docking with AutoDock4. https://doi.org/10.1007/978-1-4939-9752-7_9
  4. Chen, L., Liu, W.-G., Xiong, F., Ma, C., Sun, C., Zhu, Y.-R., Wang, Z.-H. (2021). 3D-QSAR, molecular docking and molecular dynamics simulations analyses of a series of heteroaryldihydropyrimidine derivatives as hepatitis B virus capsid assembly inhibitors. New Journal of Chemistry, 45(47), 22062–22076. https://doi.org/10.1039/D1NJ02542B
  5. Chtourou, Y., Aouey, B., Aroui, S., Kebieche, M., & Fetoui, H. (2016). Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat. Chemico-Biological Interactions, 243, 1–9. https://doi.org/10.1016/j.cbi.2015.11.019
  6. Chuang, S.-C., Vecchia, C. La, & Boffetta, P. (2009). Liver cancer: Descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Letters, 286(1), 9–14. https://doi.org/10.1016/j.canlet.2008.10.040
  7. Cole, A. G. (2016). Modulators of HBV capsid assembly as an approach to treating hepatitis B virus infection. Current Opinion in Pharmacology, 30, 131–137. https://doi.org/10.1016/j.coph.2016.08.004
  8. Du, X., Li, Y., Xia, Y. L., Ai, S. M., Liang, J., Sang, P.,Liu, S. Q. (2016). Insights into protein–ligand interactions: Mechanisms, models, and methods. International Journal of Molecular Sciences, 17(2), 1–34. https://doi.org/10.3390/ijms17020144
  9. Fadholly, A., Ansori, A. N. M., & Sucipto, T. H. (2020). An overview of naringin: Potential anticancer compound of Citrus fruits. Research Journal of Pharmacy and Technology, 13(11), 5613–5619. https://doi.org/https://doi.org/10.5958/0974-360X.2020.00979.8
  10. Fatchur, R., & Putra, W. E. (2020). Short Communication: The bioinformatics perspective of Foeniculum vulgare fruit’s bioactive compounds as natural anti-hyperglycemic against alpha-glucosidase. Biodiversitas Journal of Biological Diversity, 22(1). https://doi.org/10.13057/biodiv/d220111
  11. Firdayani, Kusumaningrum, S., & Miranti, Y. R. (2017). Potensi Senyawa Bioaktif Tanaman Genus Phyllanthus Sebagai Inhibitor Replikasi Virus Hepatitis B. Jurnal Bioteknologi & Biosains Indonesia (JBBI), 4(2), 85. Retrieved from http://ejurnal.bppt.go.id/index.php/JBBI/article/view/2589
  12. Hanif, A. U., Lukis, P. A., & Fadlan, A. (2020). Pengaruh Minimisasi Energi MMFF94 dengan MarvinSketch dan Open Babel PyRx pada Penambatan Molekular Turunan Oksindola Tersubstitusi. Alchemy, 8(2), 33–40. https://doi.org/10.18860/al.v8i2.10481
  13. Hazarika, I., Mukundan, G. K., Sundari, P. S., & Laloo, D. (2021). Journey of Hydrocotyle sibthorpioides Lam.: From traditional utilization to modern therapeutics—A review. Phytotherapy Research, 35(4), 1847–1871. https://doi.org/10.1002/ptr.6924
  14. Heidary Moghaddam, R., Samimi, Z., Moradi, S. Z., Little, P. J., Xu, S., & Farzaei, M. H. (2020). Naringenin and naringin in cardiovascular disease prevention: A preclinical review. European Journal of Pharmacology, 887, 173535. https://doi.org/10.1016/j.ejphar.2020.173535
  15. Hu, Y., Ye, Y.-Z., Ye, L.-J., Wang, X.-H., & Yu, H. (2019). Efficacy and safety of interferon alpha-2b versus pegylated interferon alpha-2a monotherapy in children with chronic hepatitis B: a real-life cohort study from Shanghai, China. World Journal of Pediatrics, 15(6), 595–600. https://doi.org/10.1007/s12519-019-00303-w
  16. Husain, D. R., Wardhani, R., & Erviani, A. E. (2022). Antibacterial activity of bacteria isolated from earthworm (Pheretima sp.) gut against Salmonella typhi and Staphylococcus aureus: in vitro experiments supported by computational docking. Biodiversitas Journal of Biological Diversity, 23(2). https://doi.org/10.13057/biodiv/d230257
  17. Husin, F., Chan, Y. Y., Gan, S. H., Sulaiman, S. A., & Shueb, R. H. (2015). The Effect of Hydrocotyle sibthorpioides Lam. Extracts on In Vitro Dengue Replication. Evidence-Based Complementary and Alternative Medicine, 2015, 1–9. https://doi.org/10.1155/2015/596109
  18. Jain, M., & Parmar, H. S. (2011). Evaluation of antioxidative and anti-inflammatory potential of hesperidin and naringin on the rat air pouch model of inflammation. Inflammation Research, 60(5), 483–491. https://doi.org/10.1007/s00011-010-0295-0
  19. Jones, S. A., & Hu, J. (2013). Hepatitis B virus reverse transcriptase: diverse functions as classical and emerging targets for antiviral intervention. Emerging Microbes & Infections, 2(1), 1–11. https://doi.org/10.1038/emi.2013.56
  20. Kanda, T., Goto, T., Hirotsu, Y., Moriyama, M., & Omata, M. (2019). Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review. International Journal of Molecular Sciences, 20(6), 1358. https://doi.org/10.3390/ijms20061358
  21. Khalil, M., Amin, M., & Lukiati, B. (2020). Analisis potensi senyawa repensol sebagai kandidat inhibitor replikasi virus hepatitis B secara in silico. In Prosiding Seminar Nasional Biotik, 8(1), 358–363. https://doi.org/https://doi.org/10.22373/pbio.v8i2.9669.
  22. Khalil, M., Rosadha, R. S., Saputra, A. R., Akbar, M. N., Azmi, U., & Hapsari, W. K. (2020). Potensi Senyawa Bioaktif Β-Carotene Sebagai Kandidat Antivirus Hepatitis B. Jurnal Geuthèë: Penelitian Multidisiplin, 3(1), 393–399. https://doi.org/10.52626/jg.v3i1.73
  23. Kusumawati, D., Widyarti, S., Maftuch, M., & Rahayu, S. (2022). In Silico Study of Haematococcus pluvialis Biomarker Compound as Supplement to Fish Bone Remodelling. HAYATI Journal of Biosciences, 29(3), 330–342. https://doi.org/10.4308/hjb.29.3.330-342
  24. Li, H., Yan, L., Shi, Y., Lv, D., Shang, J., Bai, L., & Tang, H. (2020). Hepatitis B Virus Infection: Overview. https://doi.org/10.1007/978-981-13-9151-4_1
  25. Littlejohn, M., Locarnini, S., & Yuen, L. (2016). Origins and Evolution of Hepatitis B Virus and Hepatitis D Virus. Cold Spring Harbor Perspectives in Medicine, 6(1), a021360. https://doi.org/10.1101/cshperspect.a021360
  26. Liu, H., Xi, J., & Hu, J. (2021). Regulation of Hepatitis B Virus Replication by Cyclin Docking Motifs in Core Protein. Journal of Virology, 95(12). https://doi.org/10.1128/JVI.00230-21
  27. Ministry of Health of the Republic of Indonesia. Guide to Commemoration of World Hepatitis Day XII July 28 2021. (2021).
  28. Muljono, D. H. (2017). Epidemiology of hepatitis B and C in Republic of Indonesia. Euroasian Journal of Hepato-Gastroenterology, 7(1), 55–59. https://doi.org/https://doi.org/10.5005%2Fjp-journals-l0018-1212.
  29. National Center for Biotechnology Information. (n.d.-a). PubChem Compound Summary for CID 121488107. Retrieved December 6, 2022, from https://pubchem.ncbi.nlm.nih.gov/compound/71739468
  30. National Center for Biotechnology Information. (n.d.-b). PubChem Compound Summary for CID 442428, Naringin. Retrieved December 7, 2022, from https://pubchem.ncbi.nlm.nih.gov/compound/Naringin
  31. Pantsar, T., & Poso, A. (2018). Binding Affinity via Docking: Fact and Fiction. Molecules (Basel, Switzerland), 23(8), 1–11. https://doi.org/10.3390/molecules23081899
  32. Qiu, Z., Lin, X., Zhang, W., Zhou, M., Guo, L., Kocer, B., Zhu, W. (2017). Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors. Journal of Medicinal Chemistry, 60(8), 3352–3371. https://doi.org/10.1021/acs.jmedchem.7b00083
  33. Qiu, Z., Lin, X., Zhou, M., Liu, Y., Zhu, W., Chen, W.,Tang, G. (2016a). Design and synthesis of orally bioavailable 4-methyl heteroaryldihydropyrimidine based hepatitis B virus (HBV) capsid inhibitors. Journal of Medicinal Chemistry, 59(16), 7651–7666. https://doi.org/10.1021/acs.jmedchem.6b00879
  34. Qiu, Z., Lin, X., Zhou, M., Liu, Y., Zhu, W., Chen, W.,Tang, G. (2016b). Design and Synthesis of Orally Bioavailable 4-Methyl Heteroaryldihydropyrimidine Based Hepatitis B Virus (HBV) Capsid Inhibitors. Journal of Medicinal Chemistry, 59(16), 7651–7666. https://doi.org/10.1021/acs.jmedchem.6b00879
  35. Rivoira, M. A., Rodriguez, V., Talamoni, G., & Tolosa de Talamoni, N. (2021). New Perspectives in the Pharmacological Potential of Naringin in Medicine. Current Medicinal Chemistry, 28(10), 1987–2007. https://doi.org/10.2174/0929867327666200604171351
  36. Roy, A., Khan, A., Ahmad, I., Alghamdi, S., Rajab, B. S., Babalghith, A. O., Islam, M. R. (2022). Flavonoids a Bioactive Compound from Medicinal Plants and Its Therapeutic Applications. BioMed Research International, 2022, 1–9. https://doi.org/10.1155/2022/5445291
  37. Seeliger, D., & de Groot, B. L. (2010). Ligand docking and binding site analysis with PyMOL and Autodock/Vina. Journal of Computer-Aided Molecular Design, 24(5), 417–422. https://doi.org/10.1007/s10822-010-9352-6
  38. Sharma, S., Garg, I., Kumar, B., & Ashraf, M. Z. (2018). Comparative analysis of blind docking reproducibility. Research Journal of Life Sciences, Bioinformatics, Pharmaceutical and Chemical Sciences, 4(3), 211–222. https://doi.org/https://doi.org/10.26479/2018.0403.18
  39. Shen, C., Ding, J., Wang, Z., Cao, D., Ding, X., & Hou, T. (2020). From machine learning to deep learning: Advances in scoring functions for protein–ligand docking. WIREs Computational Molecular Science, 10(1). https://doi.org/10.1002/wcms.1429
  40. Trott, O., & Olson, A. J. (2009). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, NA-NA. https://doi.org/10.1002/jcc.21334
  41. Tseng, T.-C., Kao, J.-H., & Chen, D.-S. (2014). Peginterferon α in the treatment of chronic hepatitis B. Expert Opinion on Biological Therapy, 14(7), 995–1006. https://doi.org/10.1517/14712598.2014.907784
  42. Yan, C., Xu, X., & Zou, X. (2016). Fully Blind Docking at the Atomic Level for Protein-Peptide Complex Structure Prediction. Structure, 24(10), 1842–1853. https://doi.org/10.1016/j.str.2016.07.021
  43. Zhang, J., Gao, W., Liu, Z., Zhang, Z., & Liu, C. (2014). Systematic Analysis of Main Constituents in Rat Biological Samples after Oral Administration of the Methanol Extract of Fructus Aurantii by HPLC-ESI-MS/MS. Iranian Journal of Pharmaceutical Research : IJPR, 13(2), 493–503. Retrieved from https://pubmed.ncbi.nlm.nih.gov/25237344.