Startseite Medizin Molecular docking, molecular dynamic simulation, and ADME analysis of Moringa oleifera phytochemicals targeting NS5 protein: towards the development of novel anti-dengue therapeutics
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Molecular docking, molecular dynamic simulation, and ADME analysis of Moringa oleifera phytochemicals targeting NS5 protein: towards the development of novel anti-dengue therapeutics

  • Ashish Kumar Yadav , Neha Masarkar , Maynak Pal , Sukhes Mukherjee , Ashok Kumar , Sarika Verma und Rashmi Chowdhary EMAIL logo
Veröffentlicht/Copyright: 27. Oktober 2025
Journal of Complementary and Integrative Medicine
Aus der Zeitschrift Journal of Complementary and Integrative Medicine Band 22 Heft 4

Abstract

Objectives

Dengue virus (DENV), a single-stranded RNA virus from the Flaviviridae family, causes viral hemorrhagic fever and poses a global health threat due to limited diagnostics, treatments, and vaccines. The conserved NS5 protein, crucial for DENV replication, is a promising antiviral target. Antibody-dependent enhancement (ADE) complicates immunity, as serotype-specific antibodies may worsen infection. Moringa oleifera, rich in antiviral phytochemicals, shows potential as a DENV inhibitor by targeting proteomic, transcriptomic, and metabolomic pathways.

Methods

This study employed molecular docking with 3D PubChem structures of bioactive compounds of M. oleifera to evaluate the binding affinity with DENV-2 NS5 proteins (PDB ID: 6KR2) using AutoDock Vina, and binding modes were analyzed using Discovery Studio. Further drug-likeness, oral bioavailability, ADME, and toxicity profiles were analyzed using SwissADME, ADMETSaR, and ADMETlab 3.0 web server. Complexes were subjected to molecular dynamics simulation (MDS) analysis using Desmond Schrodinger v2019.

Results

Among the screened compounds, rhamnopyranosyl vincosamide (−9.0 kcal/mol), luteoxanthin (−8.6 kcal/mol), and luteolin (−8.3 kcal/mol) exhibited the most stable interactions and were further analyzed through molecular dynamics (MD) simulations. The results revealed that these phytochemicals interact with NS5 active-site residues, demonstrating significant inhibitory potential.

Conclusions

The study suggests that M. oleifera phytochemicals hold promise as DENV-2 NS5 inhibitors with minimal toxicity and favorable pharmacokinetic properties. These findings provide a strong foundation for further clinical investigations, potentially contributing to developing novel anti-dengue therapeutics.

Keywords: dengue virus; dengue fever; docking; MD simulation; inhibitors; cheminformatics
Corresponding author: Rashmi Chowdhary, Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, India, E-mail:

Acknowledgments

The authors gratefully acknowledge the use of computational facilities and resources provided by Department of Biochemistry, AIIMS Bhopal.

  1. Research ethics: This study did not involve human participants or animals; therefore, ethical approval was not required.

  2. Informed consent: Not applicable.

  3. Author contributions: All authors contributed equally to the conception, design, execution, and interpretation of the study. All authors have read and approved the final manuscript.

  4. Use of Large Language Models, AI and Machine Learning Tools: Large Language Models (LLMs), artificial intelligence (AI), or machine learning (ML) tools were not used for data analysis or generation of results in this study. All scientific content, interpretation, and conclusions were developed and verified by the authors.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: All data generated or analyzed during this study are included within this article. The input files for molecular docking, MD simulation trajectories, and ADME/BOILED-Egg analysis data are available from the corresponding author upon reasonable request.

References

1. Guzman, MG, Alvarez, M, Halstead, SB. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol 2013;158:1445–59. https://doi.org/10.1007/s00705-013-1645-3.Suche in Google Scholar PubMed

2. Potisopon, S, Priet, S, Collet, A, Decroly, E, Canard, B, Selisko, B. The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain. Nucleic Acids Res 2014;42:11642–56. https://doi.org/10.1093/nar/gku666.Suche in Google Scholar PubMed PubMed Central

3. Zhao, R, Wang, M, Cao, J, Shen, J, Zhou, X, Wang, D, et al.. Flavivirus: from structure to therapeutics development. Life 2021;11:615. https://doi.org/10.3390/life11070615.Suche in Google Scholar PubMed PubMed Central

4. Lim, SP, Noble, CG, Shi, PY. The dengue virus NS5 protein as a target for drug discovery. Antivir Res 2015;119:57–67. https://doi.org/10.1016/j.antiviral.2015.04.010.Suche in Google Scholar PubMed

5. Bhatt, S, Gething, PW, Brady, OJ, Messina, JP, Farlow, AW, Moyes, CL, et al.. The global distribution and burden of dengue. Nature 2013;496:504–7. https://doi.org/10.1038/nature12060.Suche in Google Scholar PubMed PubMed Central

6. Katzelnick, LC, Gresh, L, Halloran, ME, Mercado, JC, Kuan, G, Gordon, A, et al.. Antibody-dependent enhancement of severe dengue disease in humans. Science 2017;358:929–32. https://doi.org/10.1126/science.aan6836.Suche in Google Scholar PubMed PubMed Central

7. Behnam, MAM, Nitsche, C, Boldescu, V, Klein, CD. The medicinal chemistry of dengue virus. J Med Chem 2016;59:5622–49. https://doi.org/10.1021/acs.jmedchem.5b01653.Suche in Google Scholar PubMed

8. Noble, CG, Chen, YL, Dong, H, Gu, F, Lim, SP, Schul, W, et al.. Strategies for development of dengue virus inhibitors. Antivir Res 2010;85:450–62. https://doi.org/10.1016/j.antiviral.2009.12.011.Suche in Google Scholar PubMed

9. Benmansour, F, Eydoux, C, Querat, G, De Lamballerie, X, Canard, B, Alvarez, K, et al.. Novel 2-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,3,4-oxadiazole and 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole derivatives as dengue virus inhibitors targeting NS5 polymerase. Eur J Med Chem 2016;109:146–56. https://doi.org/10.1016/j.ejmech.2015.12.046.Suche in Google Scholar PubMed

10. Lim, SP, Wang, QY, Noble, CG, Chen, YL, Dong, H, Zou, B, et al.. Ten years of dengue drug discovery: progress and prospects. Antivir Res 2013;100:500–19. https://doi.org/10.1016/j.antiviral.2013.09.013.Suche in Google Scholar PubMed

11. Adawara, SN, Mamza, P, Gideon, SA, Ibrahim, A. Anti-dengue potential, molecular docking study of some chemical constituents in the leaves of Isatis tinctoria. Chem Rev Lett 2020;3:104–9. https://doi.org/10.22034/crl.2020.228931.1054.Suche in Google Scholar

12. Siddiqui, S, Upadhyay, S, Ahmad, R, Barkat, MA, Jamal, A, Alothaim, AS, et al.. Interaction of bioactive compounds of Moringa oleifera leaves with SARS-CoV-2 proteins to combat COVID-19 pathogenesis: a phytochemical and in silico analysis. Appl Biochem Biotechnol 2022;194:5918–44. https://doi.org/10.1007/s12010-022-04040-1.Suche in Google Scholar PubMed PubMed Central

13. García-Ariza, LL, Rocha-Roa, C, Padilla-Sanabria, L, Castaño-Osorio, JC. Virtual screening of drug-like compounds as potential inhibitors of the dengue virus NS5 protein. Front Chem 2022;10:637266. https://doi.org/10.3389/fchem.2022.637266.Suche in Google Scholar PubMed PubMed Central

14. Bhattarai, BR, Adhikari, B, Basnet, S, Shrestha, A, Marahatha, R, Aryal, B, et al.. In silico elucidation of potent inhibitors from natural products for nonstructural proteins of dengue virus. J Chem 2022;2022:5398239. https://doi.org/10.1155/2022/5398239.Suche in Google Scholar

15. Halder, SK, Ahmad, I, Shathi, JF, Mim, MM, Hassan, MR, Jewel, MJI, et al.. A comprehensive study to unleash the putative inhibitors of Serotype2 of dengue virus: insights from an in silico structure-based drug discovery. Mol Biotechnol 2024;66:612–25. https://doi.org/10.1007/s12033-022-00582-1.Suche in Google Scholar PubMed PubMed Central

16. Masarkar, N, Pal, M, Roy, M, Yadav, AK, Pandya, B, Lokhande, S, et al.. In-silico screening of bioactive compounds of Moringa oleifera as potential inhibitors targeting HIF-1α/VEGF/GLUT-1 pathway against breast cancer. J Compl Integr Med 2025;22:149–64. https://doi.org/10.1515/jcim-2024-0176.Suche in Google Scholar PubMed

17. Eberhardt, J, Santos-Martins, D, Tillack, AF, Forli, S. AutoDock vina 1.2.0: new docking methods, expanded force field, and python bindings. J Chem Inf Model 2021;61:3891–8. https://doi.org/10.1021/acs.jcim.1c00203.Suche in Google Scholar PubMed PubMed Central

18. Sharom, F. The P-glycoprotein efflux pump: how does it transport drugs? J Membr Biol 1997;160:161–75. https://doi.org/10.1007/s002329900305.Suche in Google Scholar PubMed

19. 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. https://doi.org/10.1038/srep42717.Suche in Google Scholar PubMed PubMed Central

20. Systèmes, D. Free download: BIOVIA discovery studio visualizer. 2020. https://discover.3ds.com/discovery-studio-visualizer-download [Accessed 10 Mar 2025].Suche in Google Scholar

21. Wu, J, Ye, HQ, Zhang, QY, Lu, G, Zhang, B, Gong, P. A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase. PLoS Pathog 2020;16:e1008484. https://doi.org/10.1371/journal.ppat.1008484.Suche in Google Scholar PubMed PubMed Central

22. El Sahili, A, Lescar, J. Dengue virus non-structural protein 5. Viruses 2017;9:91. https://doi.org/10.3390/v9040091.Suche in Google Scholar PubMed PubMed Central

23. Sultan, A. Identification and development of clock-modulating small molecules-an emerging approach to fine-tune the disrupted circadian clocks. Biol Rhythm Res 2018;50. https://doi.org/10.1080/09291016.2018.1498197.Suche in Google Scholar

24. Byrd, CM, Dai, D, Grosenbach, DW, Berhanu, A, Jones, KF, Cardwell, KB, et al.. A novel inhibitor of dengue virus replication that targets the capsid protein. Antimicrob Agents Chemother 2013;57:15–25. https://doi.org/10.1128/AAC.01429-12.Suche in Google Scholar PubMed PubMed Central

25. Sampath, A, Padmanabhan, R. Molecular targets for flavivirus drug discovery. Antivir Res 2009;81:6–15. https://doi.org/10.1016/j.antiviral.2008.08.004.Suche in Google Scholar PubMed PubMed Central

26. Tomlinson, SM, Watowich, SJ. Anthracene-based inhibitors of dengue virus NS2B-NS3 protease. Antivir Res 2011;89:127–35. https://doi.org/10.1016/j.antiviral.2010.12.006.Suche in Google Scholar PubMed PubMed Central

27. Rothan, HA, Han, HC, Ramasamy, TS, Othman, S, Rahman, NA, Yusof, R. Inhibition of dengue NS2B-NS3 protease and viral replication in vero cells by recombinant retrocyclin-1. BMC Infect Dis 2012;12:314. https://doi.org/10.3389/fphar.2022.1007310.Suche in Google Scholar PubMed PubMed Central

28. Ahmad, N, Badshah, SL, Junaid, M, Ur Rehman, A, Muhammad, A, Khan, K. Structural insights into the zika virus NS1 protein inhibition using a computational approach. J Biomol Struct Dyn 2021;39:3004–11. https://doi.org/10.1080/07391102.2020.1759453.Suche in Google Scholar PubMed

29. Lim, SP, Noble, CG, Seh, CC, Soh, TS, El Sahili, A, Chan, GKY, et al.. Potent allosteric dengue virus NS5 polymerase inhibitors: mechanism of action and resistance profiling. PLoS Pathog 2016;12:e1005737. https://doi.org/10.1371/journal.ppat.1005737.Suche in Google Scholar PubMed PubMed Central

30. Lee, MF, Wu, YS, Poh, CL. Molecular mechanisms of antiviral agents against dengue virus. Viruses 2023;15:705. https://doi.org/10.3390/v15030705.Suche in Google Scholar PubMed PubMed Central

31. Li, Q, Kang, C. Dengue virus NS4B protein as a target for developing antivirals. Front Cell Infect Microbiol 2022;12:959727. https://doi.org/10.3389/fcimb.2022.959727.Suche in Google Scholar PubMed PubMed Central

32. Rashmi, SH, Disha, KS, Sudheesh, N, Karunakaran, J, Joseph, A, Jagadesh, A, et al.. Repurposing of approved antivirals against dengue virus serotypes: an in silico and in vitro mechanistic study. Mol Divers 2024;28:2831–44. https://doi.org/10.1007/s11030-023-10716-5.Suche in Google Scholar PubMed PubMed Central

33. Cosconati, S, Forli, S, Perryman, AL, Harris, R, Goodsell, DS, Olson, AJ. Virtual screening with AutoDock: theory and practice. Expert Opin Drug Discov 2010;5:597–607. https://doi.org/10.1517/17460441.2010.484460.Suche in Google Scholar PubMed PubMed Central

34. Shimizu, H, Saito, A, Mikuni, J, Nakayama, EE, Koyama, H, Honma, T, et al.. Discovery of a small molecule inhibitor targeting dengue virus NS5 RNA-dependent RNA polymerase. PLoS Negl Trop Dis 2019;13:e0007894. https://doi.org/10.1371/journal.pntd.0007894.Suche in Google Scholar PubMed PubMed Central

35. Ullah, A, Atia-tul-Wahab, Gong, P, Mateen Khan, A, Iqbal Choudhary, M. Identification of new inhibitors of NS5 from dengue virus using saturation transfer difference (STD-NMR) and molecular docking studies. RSC Adv 2023;13:355–69. https://doi.org/10.1039/D2RA04836A.Suche in Google Scholar

36. Benet, LZ, Hosey, CM, Ursu, O, Oprea, TI. BDDCS, the rule of 5 and drugability. Adv Drug Deliv Rev 2016;101:89–98. https://doi.org/10.1016/j.addr.2016.05.007.Suche in Google Scholar PubMed PubMed Central

37. Rehman, MH, Saleem, U, Ahmad, B, Rashid, M. Phytochemical and toxicological evaluation of Zephyranthes citrina. Front Pharmacol 2022;13:1007310. https://doi.org/10.3389/fphar.2022.1007310.Suche in Google Scholar PubMed PubMed Central

38. Alici, H, Tahtaci, H, Demir, K. Design and various in silico studies of the novel curcumin derivatives as potential candidates against COVID-19 -associated main enzymes. Comput Biol Chem 2022;98:107657. https://doi.org/10.1016/j.compbiolchem.2022.107657.Suche in Google Scholar PubMed PubMed Central

39. Musarra-Pizzo, M, Pennisi, R, Ben-Amor, I, Mandalari, G, Sciortino, MT. Antiviral activity exerted by natural products against human viruses. Viruses 2021;13:828. https://doi.org/10.3390/v13050828.Suche in Google Scholar PubMed PubMed Central

40. Thakur, M, Singh, M, Kumar, S, Dwivedi, VP, Dakal, TC, Yadav, V. A reappraisal of the antiviral properties of and immune regulation through dietary phytochemicals. ACS Pharmacol Transl Sci 2023;6:1600. https://doi.org/10.1021/acsptsci.3c00178.Suche in Google Scholar PubMed PubMed Central

41. Kalepu, S, Nekkanti, V. Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sin B 2015;5:442–53. https://doi.org/10.1016/j.apsb.2015.07.003.Suche in Google Scholar PubMed PubMed Central

42. Aqil, F, Munagala, R, Jeyabalan, J, Vadhanam, MV. Bioavailability of phytochemicals and its enhancement by drug delivery systems. Cancer Lett 2013;334:133–41. https://doi.org/10.1016/j.canlet.2013.02.032.Suche in Google Scholar PubMed PubMed Central

43. Sercombe, L, Veerati, T, Moheimani, F, Wu, SY, Sood, AK, Hua, S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol 2015;6:286. https://doi.org/10.3389/fphar.2015.00286.Suche in Google Scholar PubMed PubMed Central

44. Kataoka, K, Harada, A, Nagasaki, Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev 2012;64:37–48. https://doi.org/10.1016/j.addr.2012.09.013.Suche in Google Scholar

45. Loureiro, JA, Pereira, MC. PLGA based drug carrier and pharmaceutical applications: the most recent advances. Pharmaceutics 2020;12:903. https://doi.org/10.3390/pharmaceutics12090903.Suche in Google Scholar PubMed PubMed Central

46. Mares, AG, Pacassoni, G, Marti, JS, Pujals, S, Albertazzi, L. Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology. PLoS One 2021;16:e0251821. https://doi.org/10.1371/journal.pone.0251821.Suche in Google Scholar PubMed PubMed Central

47. Behl, T, Rocchetti, G, Chadha, S, Zengin, G, Bungau, S, Kumar, A, et al.. Phytochemicals from plant foods as potential source of antiviral agents: an overview. Pharmaceuticals 2021;14:381. https://doi.org/10.3390/ph14040381.Suche in Google Scholar PubMed PubMed Central

Received: 2025-04-11
Accepted: 2025-08-27
Published Online: 2025-10-27

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Efficacy of mangosteen as local drug delivery for improving periodontal health in adults with periodontitis: a systematic review and meta-analysis of randomized controlled trials
  4. Catechins in cancer therapy: integrating traditional and complementary approaches
  5. Phytochemical innovations in oral cancer therapy: targeting oncogenic pathways with natural compounds
  6. Opinion Paper
  7. Naturopathy and the Ottawa Charter: a synergistic model for community health promotion in rural India
  8. Research Articles
  9. Investigating the therapeutic potential of medical leech and leech saliva extract in flap survival: an in vivo study using rats
  10. Alstonia boonei stem bark aqueous extract ameliorates elevated parasitemia levels, normalises blood glucose, modulates inflammatory biomarkers and enhances antioxidant status in Plasmodium berghei-infected/diabetic mice
  11. Nutritional, antioxidant, enzyme inhibitory and toxicity assessments of an herbal formulation using in vitro, ex vivo, and in vivo approaches
  12. Molecular docking, molecular dynamic simulation, and ADME analysis of Moringa oleifera phytochemicals targeting NS5 protein: towards the development of novel anti-dengue therapeutics
  13. Impact of licorice supplementation on cardiac biomarkers and histomorphological changes in rats
  14. Effects of minas frescal cheese enriched with Lactobacillus acidophilus La-05 on bone health in a preclinical model of chronic kidney disease
  15. Teratogenic effect of unregistered traditional Chinese medicine containing Atractylodis lancea radix, Glycyrrhiza glabra radix, Rheum officinale rhizome, and Angelica dahurica radix on fetal morphology of BALB/c mice
  16. Network pharmacology based investigation of the multi target mechanisms of Murraya koenigii (curry leaves) in non-alcoholic steatohepatitis (NASH)
  17. Protective effects of citronellol on Escherichia coli septicemia-derived liver lesions in Wistar rats
  18. The effects of spilanthol (SA3X) supplementation on muscle size and strength in healthy men – a randomized parallel-group placebo-controlled trial
  19. Navigating complementary and alternative medicine use, medication adherence, and herb–drug interaction risks among gout patients: a multicenter cross-sectional study in indonesia
  20. Evaluation of photobiomodulation for modulating peripheral inflammation via the lumbosacral medullary region
  21. Traditional alternative and complementary medicine: a review of undergraduate courses and curricula in Peru
  22. Congress Abstracts
  23. Natural Health Products Research Society of Canada Natural Health Products and Cancer Mini-Symposium 2025
https://doi.org/10.1515/jcim-2025-0132
Schlagwörter für diesen Artikel
dengue virus; dengue fever; docking; MD simulation; inhibitors; cheminformatics

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Efficacy of mangosteen as local drug delivery for improving periodontal health in adults with periodontitis: a systematic review and meta-analysis of randomized controlled trials
  4. Catechins in cancer therapy: integrating traditional and complementary approaches
  5. Phytochemical innovations in oral cancer therapy: targeting oncogenic pathways with natural compounds
  6. Opinion Paper
  7. Naturopathy and the Ottawa Charter: a synergistic model for community health promotion in rural India
  8. Research Articles
  9. Investigating the therapeutic potential of medical leech and leech saliva extract in flap survival: an in vivo study using rats
  10. Alstonia boonei stem bark aqueous extract ameliorates elevated parasitemia levels, normalises blood glucose, modulates inflammatory biomarkers and enhances antioxidant status in Plasmodium berghei-infected/diabetic mice
  11. Nutritional, antioxidant, enzyme inhibitory and toxicity assessments of an herbal formulation using in vitro, ex vivo, and in vivo approaches
  12. Molecular docking, molecular dynamic simulation, and ADME analysis of Moringa oleifera phytochemicals targeting NS5 protein: towards the development of novel anti-dengue therapeutics
  13. Impact of licorice supplementation on cardiac biomarkers and histomorphological changes in rats
  14. Effects of minas frescal cheese enriched with Lactobacillus acidophilus La-05 on bone health in a preclinical model of chronic kidney disease
  15. Teratogenic effect of unregistered traditional Chinese medicine containing Atractylodis lancea radix, Glycyrrhiza glabra radix, Rheum officinale rhizome, and Angelica dahurica radix on fetal morphology of BALB/c mice
  16. Network pharmacology based investigation of the multi target mechanisms of Murraya koenigii (curry leaves) in non-alcoholic steatohepatitis (NASH)
  17. Protective effects of citronellol on Escherichia coli septicemia-derived liver lesions in Wistar rats
  18. The effects of spilanthol (SA3X) supplementation on muscle size and strength in healthy men – a randomized parallel-group placebo-controlled trial
  19. Navigating complementary and alternative medicine use, medication adherence, and herb–drug interaction risks among gout patients: a multicenter cross-sectional study in indonesia
  20. Evaluation of photobiomodulation for modulating peripheral inflammation via the lumbosacral medullary region
  21. Traditional alternative and complementary medicine: a review of undergraduate courses and curricula in Peru
  22. Congress Abstracts
  23. Natural Health Products Research Society of Canada Natural Health Products and Cancer Mini-Symposium 2025
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2026 De Gruyter Brill
Heruntergeladen am 10.1.2026 von https://www.degruyterbrill.com/document/doi/10.1515/jcim-2025-0132/pdf
Button zum nach oben scrollen