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Abstract

Influenza A (H1N1) remains a persistent threat due to its rapid genetic mutation and resistance to antiviral drugs like Tamiflu. peels (chen-pi) are traditionally used in medicine and contain flavonoids with potential antiviral properties. However, the impact of different processing methods on its antiviral activity is not well understood. This study aims to evaluate the anti-influenza activity of processed peels using assays and computational methods, including network pharmacology and molecular docking, and to identify key bioactive compounds and target interactions. Three processing methods (soil, bran, and vinegar) were applied to peels, and their ethanol and water extracts were tested for anti-influenza activity using an MDCK cell model. Network pharmacology analysis identified potential target genes, and molecular docking assessed the binding affinity of hesperidin and narirutin to H1N1 nucleoprotein and key host proteins. Soil-processed ethanol extracts showed the highest anti-influenza activity (56.60±5.91%), followed by bran-processed water extracts (40.49±7.48%). Network pharmacology identified 11 target genes associated with the antiviral effect, with three key targets, including DOT1L, F2, and MMP2, playing significant roles. Molecular docking revealed that hesperidin and narirutin had higher binding affinities to DOT1L, F2, MMP2, and H1N1 nucleoprotein than Tamiflu, suggesting their potential as effective H1N1 treatments. The soil-processed ethanol extracts demonstrated notably superior anti-influenza activity, potentially due to enhanced interactions between bioactive compounds and soil-derived nutrients, thereby increasing pharmacological efficacy. Network pharmacology identified DOT1L, F2, and MMP2 as key target genes linked to antiviral activity, suggesting complex antiviral mechanisms involving host-pathogen interactions. Molecular docking analysis confirmed that hesperidin and narirutin had stronger binding affinities to these targets and H1N1 nucleoprotein compared to Tamiflu. These findings support peel extracts, particularly soil-processed ethanol extracts, as promising candidates for antiviral therapeutics and traditional medicinal applications, warranting further exploration for clinical use and development as alternative antiviral agents. This study highlights the importance of processing methods in optimizing the antiviral properties of peels. The findings support its application in traditional medicine and antiviral drug development, particularly as a potential alternative to existing antiviral treatments.

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2026-01-23
2026-01-29

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References

  1. Singh I.P. Gore D. Karkhele S. Vairappan C. Columbia. SC University of South Carolina 2013 10.1007/978‑981‑99‑2302‑1_12
    [Google Scholar]
  2. Shehata M.G. Awad T.S. Asker D. El Sohaimy S.A. Curr. Res. Food Sci. 2021 4 326 10.1016/j.crfs.2021.05.001
    [Google Scholar]
  3. Jaafar Ajeena S. Mohammed Khalaf Al-Zaidi R. Thafir Hadi M. Malallah Ghazal M. Cell. Mol. Biol. 2024 70 10 161 166 10.14715/cmb/2024.70.10.21 39605110
    [Google Scholar]
  4. Chen Q. Wang D. Tan C. Hu Y. Sundararajan B. Zhou Z. Plants 2020 9 2 196 10.3390/plants9020196 32033423
    [Google Scholar]
  5. Liu S. Lou Y. Li Y. Zhang J. Li P. Yang B. Gu Q. Front. Nutr. 2022 9 968604 10.3389/fnut.2022.968604 35923210
    [Google Scholar]
  6. Tsai P.W. Rogio K.G.G. Hsieh C.Y. Cruz K.A.D.C. Lee C.J. Hsueh C.C. Huang T-N. Lu W-Z. Xie Z-L. Jheng Y-N. Chen B-Y. J. Taiwan Inst. Chem. Eng. 2023 143 104690 10.1016/j.jtice.2023.104690
    [Google Scholar]
  7. Chandimala U.R. Ajtony Z. Sik B. BIO Web Conf 2024 125 2004 10.1051/bioconf/202412502004
    [Google Scholar]
  8. Ji Z. Deng W. Chen D. Liu Z. Shen Y. Dai J. Zhou H. Zhang M. Xu H. Dai B. Heliyon 2024 10 5 e26862 10.1016/j.heliyon.2024.e26862 38486739
    [Google Scholar]
  9. Choi S.S. Lee S.H. Lee K.A. Antioxidants 2022 11 8 1618 10.3390/antiox11081618 36009336
    [Google Scholar]
  10. Pyrzynska K. Nutrients 2022 14 12 2387 10.3390/nu14122387 35745117
    [Google Scholar]
  11. Mitra S. Lami M.S. Uddin T.M. Das R. Islam F. Anjum J. Hossain M.J. Emran T.B. Biomed. Pharmacother. 2022 150 112932 10.1016/j.biopha.2022.112932 35413599
    [Google Scholar]
  12. Liu Y. Li X. Chen C. Leng A. Qu. J. Chin. Med. 2021 16 1 143 10.1186/s13020‑021‑00554‑8 34952619
    [Google Scholar]
  13. Latosińska M. Latosińska J.N. Molecules 2024 29 2 441 10.3390/molecules29020441 38257352
    [Google Scholar]
  14. Ren Y. Wan L. Cao S. Mol. Divers. 2024 28 3 1323 1333 10.1007/s11030‑023‑10659‑x 37268742
    [Google Scholar]
  15. Chupakhin O.N. Rusinov V.L. Varaksin M.V. Ulomskiy E.N. Savateev K.V. Butorin I.I. Du W. Sun Z. Charushin V.N. Int. J. Mol. Sci. 2022 23 23 14537 10.3390/ijms232314537 36498864
    [Google Scholar]
  16. Xiong R. Zhang L. Li S. Sun Y. Ding M. Wang Y. Zhao Y. Wu Y. Shang W. Jiang X. Shan J. Shen Z. Tong Y. Xu L. Chen Y. Liu Y. Zou G. Lavillete D. Zhao Z. Wang R. Zhu L. Xiao G. Lan K. Li H. Xu K. Protein Cell 2020 11 10 723 739 10.1007/s13238‑020‑00768‑w 32754890
    [Google Scholar]
  17. Elumalai G. Anand D. Sunkar S. World of Sci. J. 2025 7 4 1 15 10.3892/wasj.2025.343
    [Google Scholar]
  18. Maurer D.P. Vu M. Schmidt A.G. Immunity 2025 58 3 716 727.e6 10.1016/j.immuni.2025.02.006 40023162
    [Google Scholar]
  19. Gu R. Zhao F. Li Q. Hou L. Liu G. Sun X. Du J. Fang B. Microorganisms 2025 13 2 450 10.3390/microorganisms13020450 40005815
    [Google Scholar]
  20. Su J. Chen X. Xie Y. Li M. Shang Q. Zhang D. Cai X. Liu H. Huang H. Zheng C. Han L. J. Ethnopharmacol 2024 318 Pt B 117011 10.1016/j.jep.2023.117011 37567423
    [Google Scholar]
  21. Tsai P.W. Aledia M.R.G.G. De Castro-Cruz K.A. Garcia P.J.B. Shen C.J. Hsueh C.C. Chen C-Y. Chen B-Y. Sustain. Chem. Pharm. 2023 34 101141 10.1016/j.scp.2023.101141
    [Google Scholar]
  22. Chen Z. Ye S.Y. Zhu R.G. Pharm. Biol. 2020 58 1 561 573 10.1080/13880209.2020.1778740 32615903
    [Google Scholar]
  23. Tsai P.W. Hsieh C.Y. Ting J.U. Ciou Y.R. Lee C.J. Hsieh C.L. Lien T.K. Hsueh C.C. Chen B.Y. J. Taiwan Inst. Chem. Eng. 2022 135 104365 10.1016/j.jtice.2022.104365 35578714
    [Google Scholar]
  24. Tsai P.W. Tayo L.L. Ting J.U. Hsieh C.Y. Lee C.J. Chen C.L. Yang H.C. Tsai H.Y. Hsueh C.C. Chen B.Y. Ind. Crops Prod. 2023 191 115944 10.1016/j.indcrop.2022.115944 36405420
    [Google Scholar]
  25. Chen Y.H. Hsieh C.Y. Chiou C.T. Caro E.J.G.V. Tayo L.L. Tsai P.W. Mar. Drugs 2025 23 4 149 10.3390/md23040149 40278270
    [Google Scholar]
  26. Xu J. Luo Q. Huang Y. Li J. Ye W. Yan R. Zhou X. He Z. Liu G. Zhu Q. Emerg. Microbes Infect. 2024 13 1 2429627 10.1080/22221751.2024.2429627 39530458
    [Google Scholar]
  27. Márquez Domínguez L. Márquez Matla K. Reyes Leyva J. Vallejo Ruíz V. Santos López G. Cell. Mol. Biol. 2023 69 13 16 23 10.14715/cmb/2023.69.13.3 38158694
    [Google Scholar]
  28. Panthi S. Hong J.Y. Satange R. Yu C.C. Li L.Y. Hou M.H. Int. J. Biol. Macromol. 2024 282 Pt 4 136996 10.1016/j.ijbiomac.2024.136996 39486729
    [Google Scholar]
  29. Quignon E. Ferhadian D. Hache A. Vivet-Boudou V. Isel C. Printz-Schweigert A. Donchet A. Crépin T. Marquet R. Viruses 2024 16 3 421 10.3390/v16030421 38543786
    [Google Scholar]
  30. Kulasinghe A. Tan C.W. Ribeiro dos Santos Miggiolaro A.F. Monkman J. SadeghiRad, H.; Bhuva, D.D.; Motta Junior, J.S.; Busatta Vaz de Paula, C.; Nagashima, S.; Baena, C.P.; Souza-Fonseca-Guimaraes, P.; de Noronha, L.; McCulloch, T.; Rossi, G.R.; Cooper, C.; Tang, B.; Short, K.R.; Davis, M.J.; Souza-Fonseca-Guimaraes, F.; Belz, G.T.; O’Byrne. K. Eur Respir. J. 2022 59 6 2101881 10.1183/13993003.01881‑2021 34675048
    [Google Scholar]
  31. A’laa E. Hussein S.A. Ali H.A. J. Adv. Vet. Res. 2024 14 547 552
    [Google Scholar]
  32. Tobaruela E.C. Brasili E. Zeraik L. Milenkovic D. Hassimotto N.M.A. Lajolo F.M. Food Funct. 2024 15 2 1031 1049 10.1039/D3FO04091G 38193367
    [Google Scholar]
  33. Tan Y. Qiao Y. Chen Z. Liu J. Guo Y. Tran T. Tan K.S. Wang D.Y. Yan Y. Front. Cell Dev. Biol. 2020 8 223 10.3389/fcell.2020.00223 32300593
    [Google Scholar]
  34. Zhao Z. Li J. Feng Y. Kang X. Li Y. Chen Y. Li W. Yang W. Zhao L. Huang S. Zhang S. Jiang T. Viruses 2023 15 8 1646 10.3390/v15081646 37631988
    [Google Scholar]
  35. Tian M. Han Y.B. Zhao C.C. Liu L. Zhang F.L. Diabetol. Metab. Syndr. 2021 13 1 50 10.1186/s13098‑021‑00664‑1 33926520
    [Google Scholar]
  36. Li G. Song Z. Ru Y. Zhang J. Luo L. Yang W. Wu H. Jin H. Bao X. Wei D. Yan Z. Qu H. Zhu Z. Xue X. Zhou G. Exploration 2023 3 5 20220141 10.1002/EXP.20220141 37933289
    [Google Scholar]
  37. Zhang S. Huo C. Xiao J. Fan T. Zou S. Qi P. Sun L. Wang M. Hu Y. Virology 2019 537 110 120 10.1016/j.virol.2019.08.023 31493649
    [Google Scholar]
  38. Wudtiwai B. Makeudom A. Krisanaprakornkit S. Pothacharoen P. Kongtawelert P. Molecules 2021 26 17 5345 10.3390/molecules26175345 34500779
    [Google Scholar]
  39. Wu M. Mu C. Yang H. Wang Y. Ma P. Li S. Wang Z. Lan T. Mol. Biol. Rep. 2024 51 1 140 10.1007/s11033‑023‑09037‑5 38236447
    [Google Scholar]
  40. Chen P. Li C. Chen L. Li X. Zhu S. Eur. J. Med. Chem. 2024 277 116758 10.1016/j.ejmech.2024.116758 39151273
    [Google Scholar]
  41. Luo L. Jiang J. Wang C. Fitzgerald M. Hu W. Zhou Y. Zhang H. Chen S. Acta Pharm. Sin. B 2020 10 7 1192 1204 10.1016/j.apsb.2020.05.007 32834949
    [Google Scholar]
  42. Sun Y. Liu K. Vet. Sci. 2024 11 11 555 10.3390/vetsci11110555 39591329
    [Google Scholar]
  43. Küçükler S. Çomaklı S. Özdemir S. Çağlayan C. Kandemir F.M. Environ. Toxicol. 2021 36 8 1600 1617 10.1002/tox.23156 33908150
    [Google Scholar]
  44. Wei Z. Gao R. Sun Z. Yang W. He Q. Wang C. Zhang J. Zhang X. Guo L. Wang S. J. Med. Virol. 2023 95 5 e28790 10.1002/jmv.28790 37212338
    [Google Scholar]
  45. Westera L. Jennings A.M. Maamary J. Schwemmle M. García-Sastre A. Bortz E. Adv. Virol. 2019 2019 1 11 10.1155/2019/8512363 31015836
    [Google Scholar]
  46. Xin X. Li Y. Liu H. Sci. Rep. 2020 10 1 19426 10.1038/s41598‑020‑76156‑5 33173100
    [Google Scholar]
  47. Jung S.B. Choi G. Kim H.J. Moon K.S. Lee G. Na K.H. Kwon Y.M. Moon J. Shin M.Y. Yu J.Y. Baek Y.B. Park J.G. Park S.I. Microorganisms 2024 12 4 677 10.3390/microorganisms12040677 38674621
    [Google Scholar]
  48. Daina A. Michielin O. Zoete V. Nucleic Acids Res. 2019 47 W1 W357 W364 10.1093/nar/gkz382 31106366
    [Google Scholar]
  49. Safran M. Rosen N. Twik M. Practical Guide to Life. Science Databases. Springer 2021 27 56
    [Google Scholar]
  50. Szklarczyk D. Gable A.L. Lyon D. Junge A. Wyder S. Huerta-Cepas J. Simonovic M. Doncheva N.T. Morris J.H. Bork P. Jensen L.J. Mering C. Nucleic Acids Res. 2019 47 D1 D607 D613 10.1093/nar/gky1131 30476243
    [Google Scholar]
  51. Raudvere U. Kolberg L. Kuzmin I. Arak T. Adler P. Peterson H. Vilo J. Nucleic Acids Res. 2019 47 W1 W191 W198 10.1093/nar/gkz369 31066453
    [Google Scholar]
  52. Aleksander S.A. Balhoff J. Carbon S. Cherry J.M. Drabkin H.J. Ebert D. Feuermann M. Gaudet P. Harris N.L. Hill D.P. Lee R. Mi H. Moxon S. Mungall C.J. Muruganugan A. Mushayahama T. Sternberg P.W. Thomas P.D. Van Auken K. Ramsey J. Siegele D.A. Chisholm R.L. Fey P. Aspromonte M.C. Nugnes M.V. Quaglia F. Tosatto S. Giglio M. Nadendla S. Antonazzo G. Attrill H. dos Santos G. Marygold S. Strelets V. Tabone C.J. Thurmond J. Zhou P. Ahmed S.H. Asanitthong P. Luna Buitrago D. Erdol M.N. Gage M.C. Ali Kadhum M. Li K.Y.C. Long M. Michalak A. Pesala A. Pritazahra A. Saverimuttu S.C.C. Su R. Thurlow K.E. Lovering R.C. Logie C. Oliferenko S. Blake J. Christie K. Corbani L. Dolan M.E. Drabkin H.J. Hill D.P. Ni L. Sitnikov D. Smith C. Cuzick A. Seager J. Cooper L. Elser J. Jaiswal P. Gupta P. Jaiswal P. Naithani S. Lera-Ramirez M. Rutherford K. Wood V. De Pons J.L. Dwinell M.R. Hayman G.T. Kaldunski M.L. Kwitek A.E. Laulederkind S.J.F. Tutaj M.A. Vedi M. Wang S.J. D’Eustachio P. Aimo L. Axelsen K. Bridge A. Hyka-Nouspikel N. Morgat A. Aleksander S.A. Cherry J.M. Engel S.R. Karra K. Miyasato S.R. Nash R.S. Skrzypek M.S. Weng S. Wong E.D. Bakker E. Berardini T.Z. Reiser L. Auchincloss A. Axelsen K. Argoud-Puy G. Blatter M.C. Boutet E. Breuza L. Bridge A. Casals-Casas C. Coudert E. Estreicher A. Livia Famiglietti M. Feuermann M. Gos A. Gruaz-Gumowski N. Hulo C. Hyka-Nouspikel N. Jungo F. Le Mercier P. Lieberherr D. Masson P. Morgat A. Pedruzzi I. Pourcel L. Poux S. Rivoire C. Sundaram S. Bateman A. Bowler-Barnett E. Bye-A-Jee H. Denny P. Ignatchenko A. Ishtiaq R. Lock A. Lussi Y. Magrane M. Martin M.J. Orchard S. Raposo P. Speretta E. Tyagi N. Warner K. Zaru R. Diehl A.D. Lee R. Chan J. Diamantakis S. Raciti D. Zarowiecki M. Fisher M. James-Zorn C. Ponferrada V. Zorn A. Ramachandran S. Ruzicka L. Westerfield M. Aleksander S.A. Balhoff J. Carbon S. Cherry J.M. Drabkin H.J. Ebert D. Feuermann M. Gaudet P. Harris N.L. Hill D.P. Lee R. Mi H. Moxon S. Mungall C.J. Muruganugan A. Mushayahama T. Sternberg P.W. Thomas P.D. Van Auken K. Ramsey J. Siegele D.A. Chisholm R.L. Fey P. Aspromonte M.C. Nugnes M.V. Quaglia F. Tosatto S. Giglio M. Nadendla S. Antonazzo G. Attrill H. dos Santos G. Marygold S. Strelets V. Tabone C.J. Thurmond J. Zhou P. Ahmed S.H. Asanitthong P. Luna Buitrago D. Erdol M.N. Gage M.C. Ali Kadhum M. Li K.Y.C. Long M. Michalak A. Pesala A. Pritazahra A. Saverimuttu S.C.C. Su R. Thurlow K.E. Lovering R.C. Logie C. Oliferenko S. Blake J. Christie K. Corbani L. Dolan M.E. Drabkin H.J. Hill D.P. Ni L. Sitnikov D. Smith C. Cuzick A. Seager J. Cooper L. Elser J. Jaiswal P. Gupta P. Jaiswal P. Naithani S. Lera-Ramirez M. Rutherford K. Wood V. De Pons J.L. Dwinell M.R. Hayman G.T. Kaldunski M.L. Kwitek A.E. Laulederkind S.J.F. Tutaj M.A. Vedi M. Wang S-J. D’Eustachio P. Aimo L. Axelsen K. Bridge A. Hyka-Nouspikel N. Morgat A. Aleksander S.A. Cherry J.M. Engel S.R. Karra K. Miyasato S.R. Nash R.S. Skrzypek M.S. Weng S. Wong E.D. Bakker E. Berardini T.Z. Reiser L. Auchincloss A. Axelsen K. Argoud-Puy G. Blatter M-C. Boutet E. Breuza L. Bridge A. Casals-Casas C. Coudert E. Estreicher A. Livia Famiglietti M. Feuermann M. Gos A. Gruaz-Gumowski N. Hulo C. Hyka-Nouspikel N. Jungo F. Le Mercier P. Lieberherr D. Masson P. Morgat A. Pedruzzi I. Pourcel L. Poux S. Rivoire C. Sundaram S. Bateman A. Bowler-Barnett E. Bye-A-Jee H. Denny P. Ignatchenko A. Ishtiaq R. Lock A. Lussi Y. Magrane M. Martin M.J. Orchard S. Raposo P. Speretta E. Tyagi N. Warner K. Zaru R. Diehl A.D. Lee R. Chan J. Diamantakis S. Raciti D. Zarowiecki M. Fisher M. James-Zorn C. Ponferrada V. Zorn A. Ramachandran S. Ruzicka L. Westerfield M. Genetics 2023 224 1 iyad031 10.1093/genetics/iyad031 36866529
    [Google Scholar]
  53. Kanehisa M. Furumichi M. Sato Y. Ishiguro-Watanabe M. Tanabe M. Nucleic Acids Res. 2021 49 D1 D545 D551 10.1093/nar/gkaa970 33125081
    [Google Scholar]
  54. National Center for Biotechnology Information . PubChem Compound Summary for CID 10621, Hesperidin 2025 Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Hesperidin
    [Google Scholar]
  55. National Center for Biotechnology Information PubChem Substance Record for SID 135043891, Narirutin, Source: ChemIDplus; 2025 Available from: https://pubchem.ncbi.nlm.nih.gov/substance/135043891
    [Google Scholar]
  56. National Center for Biotechnology Information PubChem Compound Summary for CID 65028, Oseltamivir 2025 Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Oseltamivir
    [Google Scholar]
  57. Zima V. Albiñana C.B. Rojíková K. Pokorná J. Pachl P. Řezáčová P. Hudlicky J. Navrátil V. Majer P. Konvalinka J. Kožíšek M. Machara A. Bioorg. Med. Chem. 2019 27 13 2935 2947 10.1016/j.bmc.2019.05.024 31128993
    [Google Scholar]
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In vitro and Computational Studies on the Anti-H1N1 Activity of Processed Citrus reticulata Peels
Bentham Science Publishers ; https://doi.org/10.2174/0115701786400594251029055325
/content/journals/loc/10.2174/0115701786400594251029055325
/content/journals/loc/10.2174/0115701786400594251029055325
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  • Article Type:     Research Article
Keywords: Citrus reticulata peels ; Molecular docking ; Anti-H1N1 ; Tamiflu ; hesperidin ; Narirutin ; in vitro

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