Skip to main content
SpringerLink
Log in

Discovery of a new sesquiterpenoid from Phellinus ignarius with antiviral activity against influenza virus

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Seven natural products, including one new sesquiterpenoid (eudesm-1β, 6α, 11-triol, compound 1), one ergosta -4, 6, 8(14), 22-tetraen-3-one (compound 2), four polyphenols (compounds 3, 4, 5, 6), and one pyrone (3-hydroxy-2-methyl-4-pyrone, compound 7) were isolated from cultures of Phellinus ignarius by column chromatography. The detailed structure of compound 1 was determined using a combination of one- and two-dimensional nuclear magnetic resonance, mass spectrometry and infrared spectroscopy. The antiviral activity of these compounds against H5N1 influenza A virus was investigated using an MTT colorimetric assay system in Madin-Darby canine kidney cells. The results indicate that compound 1 possesses significant ability to inhibit influenza virus. The 50 % effective concentration was 0.14 ± 0.04 μM. Molecular modeling further suggested that the anti-influenza virus activity of this compound was partially attributed to the interactions of hydroxyl groups with an amino acid residue (Asn 170) of neuraminidase (NA) at the binding site. Moreover, the results of enzyme inhibition assays indicated that 50 % inhibition of NA was achieved by compound 1 at a concentration of 0.657 ± 0.325 mg/mL, which suggested that compound 1 is likely to interact with the NA enzyme.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cho HG, Choi JH, Kim WH, Hong HK, Yoon MH, Jho EH, Kang C, Lim YH (2012) High prevalence of amantadine-resistant influenza A virus isolated in Gyeonggi Province, South Korea, during 2005–2010. Arch Virol. doi:10.1007/s00705-012-1482-9

    Google Scholar 

  2. Yeh J-Y, Coumar MS, Horng J-T et al (2010) Anti-influenza drug discovery: structure-activity relationship and mechanistic insight into novel angelicin derivatives. J Med Chem 53:1519

    Article  PubMed  CAS  Google Scholar 

  3. Ge S, Zheng D, Zhao Y et al (2012) Evaluating viral interference between influenza virus and newcastle disease virus using real-time reverse transcription–polymerase chain reaction in chicken eggs. Virol J 9:128. doi:10.1186/1743-422X-9-128

    Article  PubMed Central  PubMed  Google Scholar 

  4. Dermody TS, Sandri-Goldin RM, Shenk T (2013) A New Determinant of H5N1 Influenza Virus Pathogenesis in Mammals. J Virol. doi:10.1128/JVI.00474-13

  5. Malakoff D, Enserink M (2013) Dual use research. New U.S. rules increase oversight of H5N1 studies, other risky science. Science 339(6123):1025

    Article  PubMed  CAS  Google Scholar 

  6. He P, Geng L, Wang J, Wang Z, Mao D, Xu C (2012) Purification, characterization and bioactivity of an extracellular polysaccharide produced from Phellinus igniarius. Ann Microbiol. doi:10.1007/s13213-012-0427-6

    Google Scholar 

  7. Wang G, Dong L, Zhang Y (2012) Polysaccharides from Phellinus linteus inhibit cell growth and invasion and induce apoptosis in HepG2 human hepatocellular carcinoma cells. Biologia 67:247

    Article  CAS  Google Scholar 

  8. Dong W, Ning L et al (2009) Tumor-inhibitory and liver-protective effects of Phellinus igniarius extracellular polysaccharides. World J Microbiol Biotechnol 25(4):633

    Article  CAS  Google Scholar 

  9. Zou X, Guo X, Sun M (2009) pH control strategy in a shaken minibioreactor for polysaccharide production by medicinal mushroom Phellinus linteus and its anti-hyperlipemia activity. Bioprocess Biosyst Eng 32:277

    Article  PubMed  CAS  Google Scholar 

  10. Wu X, Lin S, Zhu C et al (2010) Homo- and heptanor-sterols and tremulane sesquiterpenes from cultures of Phellinus igniarius. J Nat Prod 73:1294–1300

    Article  PubMed  CAS  Google Scholar 

  11. Wu X, Lin S, Zhu C et al (2010) Constituents of cultures of fungus Phellinus igniarius. China J Chin Materia Medica 36(7):874

    Google Scholar 

  12. Dao TT, Tung BT, Nguyen PH et al (2010) C-methylated flavonoids from cleistocalyx operculatus and their inhibitory effects on novel influenza A (H1N1) neuraminidase. J Nat Prod 73:1636

    Article  CAS  Google Scholar 

  13. Motoki Takagi, Keiichiro Motohashi, Aya Nagai et al (2010) Anti-nfluenza Virus Compound from Streptomyces sp. RI18. ORGANIC LETTERS 12(20): 4664-4666

  14. Shie JJ, Fang JM et al (2011) A practical synthesis of zanamivir phosphonate congeners with potent anti-influenza activity. J Am Chem Soc 133(44):17959

    Article  PubMed  CAS  Google Scholar 

  15. Das K (2012) Antivirals targeting influenza A virus. J Med Chem. doi:10.1021/jm300455c

    PubMed Central  Google Scholar 

  16. Varghese JN, Laver WG, Colman PM (1983) Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution. Nature 303:35–40

    Article  PubMed  CAS  Google Scholar 

  17. Russell RJ, Haire LF et al (2006) The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 443(7107):45

    Article  PubMed  CAS  Google Scholar 

  18. Bao-Kai Cui, Cony Decock (2012) Phellinus castanopsidis sp. nov. (Hymenochaetaceae) from southern China, with preliminary phylogeny based on rDNA sequences. Mycol Progress. doi:10.1007/s11557-012-0839-5

  19. Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. Am J Epidemiol 27(3):493

    Google Scholar 

  20. Bing FH, Liu J et al (2009) Anti-influenza virus activity of total alkaloids from Commelina communis L. Arch Virol 154(11):1837

    Article  PubMed  CAS  Google Scholar 

  21. Kwon HJ, Kim HH, Yoon SY, Ryu YB et al (2010) In vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination. Virol J 7:307

    Article  PubMed Central  PubMed  Google Scholar 

  22. Wu QX, Shi YP, Jia ZJ (2006) Eudesmane sesquiterpenoids from the Asteraceae family. Nat Prod Rep 23:699

    Article  PubMed  CAS  Google Scholar 

  23. Ohmoto T, Ikeda K, Nomura S et al (1987) Studies on the sesquiterpenes from Ambrosia elatior LINNE. Chem Pharm Bull 35(6):2272

    Article  CAS  Google Scholar 

  24. Iijima T, Yaoita Y, Kikuchi M (2003) Five new sesquiterpenoids and a new diterpenoid from Erigeron annuus (L.) PERS., Erigeron philadelphicus L. and Erigeron sumatrensis RETZ. Chem Pharm Bull 51(5):545

    Article  PubMed  CAS  Google Scholar 

  25. Zhao Y, Yue JM, He YN et al (1997) Eleven new eudesmane derivatives from Laggera pterodonta. J Nat Prod 60:545

    Article  CAS  Google Scholar 

  26. Haruhiro F, Etsuko N, Emi O (2004) Six immunosuppressive features from an scomycete, Zopfiella longicaudata, found in a screening study monitored by immunomodulatory activity. Chem Pharm Bull 52(8):1005

    Article  Google Scholar 

  27. Zhu X, Da S, Huan L (2007) Polyphenols based on isoflavones as inhibitors of Helicobacter pylori urease. Bioorg Med Chem 15:3703–3710

    Article  PubMed  CAS  Google Scholar 

  28. Aldrich Library of 13C and 1H FT NMR Spectra (1992) 2: 180C

  29. Aldrich Library of 13C and 1H FT NMR Spectra (1992) 2: 276C, 296A

  30. Ronald B, Bhatia P (1982) Catechol O-Methyltransferase. 12. Affinity labeling the active site with the oxidation products of 5, 6-Dihydroxyindole. J Med Chem 25:263–271

    Article  Google Scholar 

  31. Aldrich Library of 13C and 1H FT NMR Spectra (1992) 1:724A

Download references

Acknowledgments

This project was financially supported by Science and Technology Development Plan of Shandong Province (No. 2010GNC10956). We are grateful for the help of Professor Ji-Kai Liu. We thank Dr. Martin Sadilek and Loren Kruse (Department of Chemistry, University of Washington, USA) for English editing. We also thank BioBioPha Co., Ltd. and National Reference Laboratory for Newcastle Disease, China Animal Health and Epidemiology Center for their contributions.

Author information

Authors and Affiliations

  1. Shandong Province Key Laboratory of Applied Mycology, School of Life Sciences, Qingdao Agricultural University, Changcheng Road 700, Chengyang, Qingdao, 266109, People’s Republic of China

    Ai-Rong Song, Xiao-Le Sun, Chao Kong, Chen Zhao, Dan Qin, Fang Huang & Song Yang

  2. Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin, 300072, People’s Republic of China

    Song Yang

Authors
  1. Ai-Rong Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Le Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chen Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dan Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Song Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Song Yang.

Additional information

A.-R. Song, X.-L. Sun, and C. Kong equally contributed to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 81 kb)

Supplementary material 2 (PPT 1075 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, AR., Sun, XL., Kong, C. et al. Discovery of a new sesquiterpenoid from Phellinus ignarius with antiviral activity against influenza virus. Arch Virol 159, 753–760 (2014). https://doi.org/10.1007/s00705-013-1857-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-013-1857-6

Keywords

Search

Navigation