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Zeylanone epoxide isolated from Diospyros anisandra stem bark inhibits influenza virus in vitro

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Abstract

Influenza virus infection is a public health problem, causing significant morbidity and mortality. Currently, zanamivir and oseltamivir are in common use, and there are already reports of antiviral resistance. Several studies have shown the antiviral potential of a wide variety of plant-based natural compounds, among them those of the quinone type. In this study, we evaluated the antiviral activity of naphthoquinones isolated from the stem bark of Diospyros anisandra, and we selected zeylanone epoxide (ZEP) to study its effects on influenza A and B viruses. Our results indicated that ZEP inhibits the replication of influenza A and B viruses, at early and middle stages of the replication cycle. Confined nuclear localization of the viral NP indicated that ZEP affects its intracellular distribution and reduces viral yield. This is the first report on the antiviral properties and possible mechanism of action of ZEP in vitro, showing its broad-spectrum activity against influenza A and B viruses.

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References

  1. Aoki-Utsubo C, Chen M, Hotta H (2018) Time-of-addition and temperature-shift assays to determine particular step(s) in the viral life cycle that is blocked by antiviral substance(s). Bio-protocol 8(9):e2830

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bodian D, Yamasaki B, Buswell R, Stearns J, White J, Kuntz D (1993) Inhibition of the fusion-inducing conformational change of influenza hemagglutinin by benzoquinones and hydroquinones. Biochem 32:2976–2978

    Article  Google Scholar 

  3. Borges R, Uc A, Quintal C, Canché G, Cáceres M (2013) A selective chemical method for the separation of quinones from the stem bark of Diospyros anisandra. Int J Curr Pharm Res 5:13–17

    Google Scholar 

  4. Bouvier N, Palese P (2008) The biology of influenza virus. Vaccine 12:49–53

    Article  CAS  Google Scholar 

  5. Burnham A, Baranovich T, Govorkova E (2013) Neuraminidase inhibitors for influenza B virus infection: Efficacy and resistance. Antiviral Res 100:520–534

    Article  CAS  PubMed  Google Scholar 

  6. CDC (2017) Types of influenza viruses. https://www.cdc.gov/flu/about/viruses/types.htm

  7. Cianci C, Gerritz S, Deminie C, Krystal M (2013) Influenza nucleoprotein: promising target for antiviral chemotherapy. Antivir Chem Chemother 23:77–91

    Article  CAS  Google Scholar 

  8. Chang S, Park J, Kim Y, Kang J, Min J (2016) A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein. Biochem Biophys Res Commun 471:282–289

    Article  CAS  PubMed  Google Scholar 

  9. Chaimayo C, Hayashi T, Underwood A, Hodges E, Takimoto T (2017) Selective incorporation of vRNP into influenza A virions determined by its specific interaction with M1 protein. Virology 505:23–32

    Article  CAS  PubMed  Google Scholar 

  10. Chavan R, Shinde B, Girkar K, Mandage R, Chowdhary A (2014) Identification of potent natural inhibitors against H1N1/A/2009 virus using in silico subtractive genomics approach and docking technology. Int J Pharm Res 6:105–113

    CAS  Google Scholar 

  11. Dayem AA, Choi HY, Kim YB, Cho S-G (2015) Antiviral effect of methylated flavonol isorhamnetin against influenza. PLoS One 10(3):e0121610

    Article  CAS  PubMed Central  Google Scholar 

  12. Dou D, Revol R, Östbye H, Wang H, Daniels R (2018) Influenza A virus cell entry, replication, virion assembly and movement. Front Immunol 9:1581–1597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Furuta Y, Takahashi K, Sangawa H, Kuno-Maekawa M, Uehara S, Nomura N, Kozaki K, Egawa H, Shiraki K (2005) Mechanism of Action of T-705 against influenza virus. Antimicrob Agents Chemother 49:981–986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hook I, Mills C, Sheridan H (2014) Bioactive naphthoquinones from higher plants. In: Rahman A (ed) Studies in natural products chemistry. Elsevier, New York, pp 119–160

    Google Scholar 

  15. Hu Y, Sneyd H, Dekant R, Wang J (2017) Influenza A virus nucleoprotein: a highly conserved multifunctional viral protein as a hot antiviral drug target. Curr Top Med Chem 17:2271–2285

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Hu Y, Zhang J, Musharrafieh R, Ma C, Hau R, Wang J (2017) Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses. Antiviral Res 145:103–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Huang F, Chen J, Zhang J, Tan L, Lu G, Luo Y, Pan T, Liang J, Li Q, Luo B, Zhang H, Lu G (2018) Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein. J Cell Mol Med 22:1826–1839

    Article  CAS  PubMed  Google Scholar 

  18. Klots L, Hou X, Jacob C (2014) 1,4-Naphthoquinones: from oxidative damage to cellular and inter-cellular signaling. Molecules 19:14902–14918

    Article  CAS  Google Scholar 

  19. Kumagai Y, Shinkai Y, Miura T, Cho A (2012) The chemical biology of naphthoquinones and its environmental implications. Annu Rev Pharmacol Toxicol 52:221–247

    Article  CAS  PubMed  Google Scholar 

  20. Kwon H, Kim H, Yoon S, Ryu Y, Chang J, Cho K, Rho M, Park S, Lee W (2010) In vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination. Virol J 7:307–316

    Article  PubMed  PubMed Central  Google Scholar 

  21. Li T, Chan M, Lee N (2015) Clinical implications of antiviral resistance in influenza. Viruses 7:4929–4944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu G, Xion S, Xiang Y, Gou C, Ge F, Yang C, Zhang Y, Wang Y, Kitazato K (2011) Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus. Arch Virol 156:1359–1369

    Article  CAS  PubMed  Google Scholar 

  23. Loregian A, Mercorelli B, Nannetti G, Compagnin C, Palù G (2014) Antiviral strategies against influenza virus: towards new therapeutic approaches. Cell Mol Life Sci 71:3659–3683

    Article  CAS  PubMed  Google Scholar 

  24. Makau J, Watanabe K, Kobayashi N (2013) Anti-influenza activity of Alchemilla mollis extract: possible virucidal activity against influenza virus particles. Drug Discov Ther 7:189–195

    CAS  PubMed  Google Scholar 

  25. McKimm-Breschkin J (2013) Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance. Influenza Other Respir Viruses 7:25–36

    Article  CAS  PubMed  Google Scholar 

  26. Nematollahi A, Aminimoghadamfarouj N, Wiart C (2012) Reviews on 1,4-naphthoquinones from Diospyros L. J Asian Nat Prod Res 14:80–88

    Article  CAS  PubMed  Google Scholar 

  27. Newman D, Cragg G (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Perwitasari O, Johnson S, Yan X, Howerth E, Shacham S, Landesman Y, Baloglu E, McCauley D, Tamir S, Tompkins M, Tripp R (2014) Verdinexor, a novel selective inhibitor of nuclear export, reduces influenza A virus replication in vitro and in vivo. J Virol 88:10228–10243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Portela A, Digard P (2002) The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol 83:723–734

    Article  CAS  PubMed  Google Scholar 

  30. Rodriguez C, Shinyashiki M, Froines J, Yu R, Fukuto J, Cho A (2004) An examination of quinone toxicity using the yeast Saccharomyces cerevisiae model system. Toxicology 201:185–196

    Article  CAS  PubMed  Google Scholar 

  31. Song J, Lee K, Seong B (2005) Antiviral effect of catechins in green tea on influenza virus. Antiviral Res 68:66–74

    Article  CAS  PubMed  Google Scholar 

  32. Sydiskis R, Owen D, Lohr J, Rosler K, Blomster R (1991) Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother 35:2463–2466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Szewczyk B, Bienkowska-Szewczyk K, Król E (2014) Introduction to molecular biology of influenza A viruses. Acta Biochim Pol 61:397–401

    Article  PubMed  Google Scholar 

  34. Uc A, Borges R, Said S, Vargas J, González F, Méndez M, Cáceres M, Molina G (2014) Naphthoquinones isolated from Diospyros anisandra exhibit potent activity against pan-resistant first-line drugs Mycobacterium tuberculosis strains. Pulm Pharmacol Ther 27:114–120

    Article  CAS  Google Scholar 

  35. Uc A, Molina GM, Said S, Méndez M, Cáceres M, Borges R (2013) A new dimeric naphthoquinone from Diospyros anisandra. Nat Prod Res 27:1174–1178

    Article  CAS  Google Scholar 

  36. WHO (2011) Manual for the laboratory diagnosis and virological surveillance of influenza. http://apps.who.int/iris/bitstream/10665/44518/1/9789241548090_eng.pdf

  37. Yang Y, Zhao D, Yuan K, Zhou G, Wang Y, Xiao Y, Wang C, Xu J, Yang W (2014) Two new dimeric naphthoquinones with neuraminidase inhibitory activity from Lithospermum erythrorhizon. Nat Prod Res 29:908–913

    Article  CAS  PubMed  Google Scholar 

  38. Yang Z, Yang Y, Wu F, Feng X (2013) Computational investigation of interaction mechanisms between juglone and influenza virus surface glycoproteins. Mol Simul 39:788–795

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by CONACYT (project number 126763). Cetina-Montejo also acknowledges CONACYT for grant number 394861. We would like to thank technician M. Cáceres-Farfán for providing technical support in the GC-MS.

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Authors and Affiliations

  1. Unidad de Biotecnología, Centro de Investigación Científica de Yucatán, Calle 43 Número 130 x 32 y 34, CP 97205, Mérida, Yucatán, México

    Lisseth Cetina-Montejo & Rocío Borges-Argáez

  2. Departamento de Virología, Centro de Investigaciones Regionales “Dr, Hideyo Nogüchi”, Calle 96 s/n x Av. Jacinto Canek y calle 47 Paseo de Las Fuentes, CP 97225, Mérida, Yucatán, México

    Guadalupe Ayora-Talavera

Authors
  1. Lisseth Cetina-Montejo
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  2. Guadalupe Ayora-Talavera
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  3. Rocío Borges-Argáez
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Correspondence to Guadalupe Ayora-Talavera or Rocío Borges-Argáez.

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Cetina-Montejo, L., Ayora-Talavera, G. & Borges-Argáez, R. Zeylanone epoxide isolated from Diospyros anisandra stem bark inhibits influenza virus in vitro. Arch Virol 164, 1543–1552 (2019). https://doi.org/10.1007/s00705-019-04223-y

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  • DOI: https://doi.org/10.1007/s00705-019-04223-y

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