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image of Investigating the Effectiveness of Natural Analogs and Different Metabolites of Curcumin for the Inhibition of the Influenza Virus Proteins in a Simulated Environment

Abstract

Background

Curcumin possesses numerous properties, including anti-influenza effects. Various natural analogs and metabolites of curcumin have been identified.

Objective

To better understand the mechanism of curcumin's anti-influenza effect, the inhibitory effect of natural analogs and secondary metabolites of curcumin on 11 influenza virus proteins was investigated in a simulated environment.

Methods

Molecular data and structural files of curcumin, its natural analogs, and secondary metabolites were retrieved from the PubChem database for conversion to PDB files. Viral protein sequences were obtained from uniprot.org, and PDB structures of proteins were predicted using an online protein structure and I-TASSER server. Using AutoDock 4.2 software, the molecular docking studies were performed.

Results

Three natural analogs of curcumin had a greater affinity to the PB1-F2 protein of the virus. The Binding Energies (BEs) of curcumin, bisdemethoxycurcumin, and demethoxycurcumin to the PB1-F2 protein were -8.28, -8.44, and -8.46 kcal/mol, respectively. Although bisdemethoxycurcumin had the lowest BE, it interacted with fewer amino acids in the active site of the protein compared to the other analogs. Curcumin metabolites were less likely to bind to influenza virus protein than curcumin.

Conclusion

Our study indicated curcumin and its analogs to have the greatest affinity to the PB1-F2 protein compared to other viral proteins. Given the role of this protein in increasing inflammation caused by influenza, curcumin may reduce inflammation in patients by affecting the function of this protein.

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2025-01-03
2025-04-17
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References

  1. Paget J. Spreeuwenberg P. Charu V. Taylor R.J. Iuliano A.D. Bresee J. Simonsen L. Viboud C. Global mortality associated with seasonal influenza epidemics: New burden estimates and predictors from the GLaMOR Project. J. Glob. Health 2019 9 2 020421 10.7189/jogh.09.020421 31673337
    [Google Scholar]
  2. Liu Q. Liu D. Yang Z. Characteristics of human infection with avian influenza viruses and development of new antiviral agents. Acta Pharmacol. Sin. 2013 34 10 1257 1269 10.1038/aps.2013.121 24096642
    [Google Scholar]
  3. Volak L.P. Hanley M.J. Masse G. Hazarika S. Harmatz J.S. Badmaev V. Majeed M. Greenblatt D.J. Court M.H. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br. J. Clin. Pharmacol. 2013 75 2 450 462 10.1111/j.1365‑2125.2012.04364.x 22725836
    [Google Scholar]
  4. Anand P. Thomas S.G. Kunnumakkara A.B. Sundaram C. Harikumar K.B. Sung B. Tharakan S.T. Misra K. Priyadarsini I.K. Rajasekharan K.N. Aggarwal B.B. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem. Pharmacol. 2008 76 11 1590 1611 10.1016/j.bcp.2008.08.008 18775680
    [Google Scholar]
  5. Valipour A. Valipour M. A review of curcumin and its role in disease prevention and treatment. J. Clin. Excell. 2017 6 1
    [Google Scholar]
  6. Chen D.Y. Shien J.H. Tiley L. Chiou S.S. Wang S.Y. Chang T.J. Lee Y.J. Chan K.W. Hsu W.L. Curcumin inhibits influenza virus infection and haemagglutination activity. Food Chem. 2010 119 4 1346 1351 10.1016/j.foodchem.2009.09.011
    [Google Scholar]
  7. Ou J.L. Mizushina Y. Wang S.Y. Chuang D.Y. Nadar M. Hsu W.L. Structure–activity relationship analysis of curcumin analogues on anti‐influenza virus activity. FEBS J. 2013 280 22 5829 5840 10.1111/febs.12503 24034558
    [Google Scholar]
  8. Farhadian S. Heidari-Soureshjani E. Hashemi-Shahraki F. Hasanpour-Dehkordi A. Uversky V.N. Shirani M. Shareghi B. Sadeghi M. Pirali E. Hadi-Alijanvand S. Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry. J. Mol. Struct. 2022 1256 132488 10.1016/j.molstruc.2022.132488 35125515
    [Google Scholar]
  9. Bruns K. Studtrucker N. Sharma A. Fossen T. Mitzner D. Eissmann A. Tessmer U. Röder R. Henklein P. Wray V. Schubert U. Structural characterization and oligomerization of PB1-F2, a proapoptotic influenza A virus protein. J. Biol. Chem. 2007 282 1 353 363 10.1074/jbc.M606494200 17052982
    [Google Scholar]
  10. Zamarin D. Ortigoza M.B. Palese P. Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice. J. Virol. 2006 80 16 7976 7983 10.1128/JVI.00415‑06 16873254
    [Google Scholar]
  11. Le Goffic R. Leymarie O. Chevalier C. Rebours E. Da Costa B. Vidic J. Descamps D. Sallenave J.M. Rauch M. Samson M. Delmas B. Transcriptomic analysis of host immune and cell death responses associated with the influenza A virus PB1-F2 protein. PLoS Pathog. 2011 7 8 e1002202 10.1371/journal.ppat.1002202 21901097
    [Google Scholar]
  12. McAuley J.L. Chipuk J.E. Boyd K.L. Van De Velde N. Green D.R. McCullers J.A. PB1-F2 proteins from H5N1 and 20 century pandemic influenza viruses cause immunopathology. PLoS Pathog. 2010 6 7 e1001014 10.1371/journal.ppat.1001014 20661425
    [Google Scholar]
  13. Košík I. Krejnusová I. Bystrická M. Poláková K. Russ G. N-terminal region of the PB1-F2 protein is responsible for increased expression of influenza A viral protein PB1. Acta Virol. 2011 55 1 45 53 10.4149/av_2011_01_45 21434704
    [Google Scholar]
  14. Sandur S.K. Pandey M.K. Sung B. Ahn K.S. Murakami A. Sethi G. Limtrakul P. Badmaev V. Aggarwal B.B. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis 2007 28 8 1765 1773 10.1093/carcin/bgm123 17522064
    [Google Scholar]
  15. Huang C. Lu H.F. Chen Y.H. Chen J.C. Chou W.H. Huang H.C. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and –independent apoptosis via Smad or Akt signaling pathways in HOS cells. BMC Complement. Med. Ther. 2020 20 1 68 10.1186/s12906‑020‑2857‑1 32126993
    [Google Scholar]
  16. Zhao F. Gong Y. Hu Y. Lu M. Wang J. Dong J. Chen D. Chen L. Fu F. Qiu F. Curcumin and its major metabolites inhibit the inflammatory response induced by lipopolysaccharide: Translocation of nuclear factor-κB as potential target. Mol. Med. Rep. 2015 11 4 3087 3093 10.3892/mmr.2014.3079 25502175
    [Google Scholar]
  17. Zhang Z.B. Luo D.D. Xie J.H. Xian Y.F. Lai Z.Q. Liu Y.H. Liu W.H. Chen J.N. Lai X.P. Lin Z.X. Su Z.R. Curcumin’s metabolites, tetrahydrocurcumin and octahydrocurcumin, possess superior anti-inflammatory effects in vivo through suppression of TAK1-NF-κB pathway. Front. Pharmacol. 2018 9 1181 10.3389/fphar.2018.01181
    [Google Scholar]
  18. Zhang Z. Luo D. Xie J. Lin G. Zhou J. Liu W. Li H. Yi T. Su Z. Chen J. Octahydrocurcumin, a final hydrogenated metabolite of curcumin, possesses superior anti-tumor activity through induction of cellular apoptosis. Food Funct. 2018 9 4 2005 2014 10.1039/C7FO02048A 29616245
    [Google Scholar]
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  • Article Type:
    Research Article
Keywords: Curcumin ; influenza virus ; secondary metabolites ; in silico ; natural analogs
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