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Abstract

Chios mastic gum (CMG), a resin of the mastic tree ( var. chia), has been used to treat multiple disorders caused by gastrointestinal malfunctions and bacterial infections for more than 2500 years. However, little is known about CMG’s antiviral activity. CMG is known to influence multiple cellular processes such as cell proliferation, differentiation and apoptosis. As virus replication is largely dependent on the host cellular metabolism, it is conceivable that CMG regulates virus infectivity. Therefore, in this study, we evaluated CMG’s potential as an antiviral drug to treat influenza A virus (IAV) infection. CMG treatment dramatically reduced the cytopathogenic effect and production of RNAs, proteins and infectious particles of IAV. Interestingly, CMG interfered with the early stage of the virus life cycle after viral attachment. Importantly, the administration of CMG greatly ameliorated morbidity and mortality in IAV-infected mice. The results suggest that CMG displays a potent anti-IAV activity by blocking the early stage of viral replication. Thus, mastic gum could be exploited as a novel therapeutic agent against IAV infection.

Funding
This study was supported by the:
  • National Research Foundation of Korea (Award NRF-2018R1A5A1025077)
    • Principle Award Recipient: Young-JinSeo
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/content/journal/jgv/10.1099/jgv.0.001550
2021-01-08
2024-10-09
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References

  1. Paraschos S, Magiatis P, Mitakou S, Petraki K, Kalliaropoulos A et al. In vitro and in vivo activities of Chios mastic gum extracts and constituents against Helicobacter pylori. Antimicrob Agents Chemother 2007; 51:551–559 [View Article][PubMed]
    [Google Scholar]
  2. Miyamoto T, Okimoto T, Kuwano M. Chemical composition of the essential oil of Mastic gum and their antibacterial activity against drug-resistant Helicobacter pylori. Nat Prod Bioprospect 2014; 4:227–231 [View Article][PubMed]
    [Google Scholar]
  3. Giaginis C, Theocharis S. Current evidence on the anticancer potential of Chios mastic gum. Nutr Cancer 2011; 63:1174–1184 [View Article][PubMed]
    [Google Scholar]
  4. Triantafyllou A, Bikineyeva A, Dikalova A, Nazarewicz R, Lerakis S et al. Anti-Inflammatory activity of Chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress. Nutr J 2011; 10:64 [View Article][PubMed]
    [Google Scholar]
  5. Spyridopoulou K, Tiptiri-Kourpeti A, Lampri E, Fitsiou E, Vasileiadis S et al. Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models. Sci Rep 2017; 7:3782 [View Article][PubMed]
    [Google Scholar]
  6. Balan KV, Demetzos C, Prince J, Dimas K, Cladaras M et al. Induction of apoptosis in human colon cancer HCT116 cells treated with an extract of the plant product, Chios mastic gum. In Vivo 2005; 19:93–102[PubMed]
    [Google Scholar]
  7. Balan KV, Prince J, Han Z, Dimas K, Cladaras M et al. Antiproliferative activity and induction of apoptosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia. Phytomedicine 2007; 14:263–272 [View Article][PubMed]
    [Google Scholar]
  8. Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 2018; 391:1285–1300 [View Article][PubMed]
    [Google Scholar]
  9. Salomon R, Webster RG. The influenza virus enigma. Cell 2009; 136:402–410 [View Article][PubMed]
    [Google Scholar]
  10. Saunders-Hastings PR, Krewski D. Reviewing the history of pandemic influenza: understanding patterns of emergence and transmission. Pathogens 2016; 5:66 [View Article][PubMed]
    [Google Scholar]
  11. Taubenberger JK, Morens DM. 1918 influenza: the mother of all pandemics. Emerg Infect Dis 2006; 12:15–22 [View Article][PubMed]
    [Google Scholar]
  12. Bahadoran A, Lee SH, Wang SM, Manikam R, Rajarajeswaran J et al. Immune responses to influenza virus and its correlation to age and inherited factors. Front Microbiol 2016; 7:1841 [View Article][PubMed]
    [Google Scholar]
  13. Krammer F. The human antibody response to influenza A virus infection and vaccination. Nat Rev Immunol 2019; 19:383–397 [View Article][PubMed]
    [Google Scholar]
  14. Allen UD, Aoki FY, Stiver HG. The use of antiviral drugs for influenza: recommended guidelines for practitioners. Can J Infect Dis Med Microbiol 2006; 17:273–284 [View Article][PubMed]
    [Google Scholar]
  15. Eiland LS, Eiland EH. Zanamivir for the prevention of influenza in adults and children age 5 years and older. Ther Clin Risk Manag 2007; 3:461–465[PubMed]
    [Google Scholar]
  16. Dharan NJ, Gubareva LV, Meyer JJ, Okomo-Adhiambo M, McClinton RC et al. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA 2009; 301:1034–1041 [View Article][PubMed]
    [Google Scholar]
  17. Heo Y, Cho Y, Ju KS, Cho H, Park KH et al. Antiviral activity of Poncirus trifoliata seed extract against oseltamivir-resistant influenza virus. J Microbiol 2018; 56:586–592 [View Article][PubMed]
    [Google Scholar]
  18. Koseki N, Kaiho M, Kikuta H, Oba K, Togashi T et al. Comparison of the clinical effectiveness of zanamivir and laninamivir octanoate for children with influenza A(H3N2) and B in the 2011-2012 season. Influenza Other Respir Viruses 2014; 8:151–158 [View Article][PubMed]
    [Google Scholar]
  19. Dimas KS, Pantazis P, Ramanujam R. Review: Chios mastic gum: a plant-produced resin exhibiting numerous diverse pharmaceutical and biomedical properties. In Vivo 2012; 26:777–785[PubMed]
    [Google Scholar]
  20. Seo YJ, Pritzl CJ, Vijayan M, Bomb K, McClain ME et al. Sphingosine kinase 1 serves as a pro-viral factor by regulating viral RNA synthesis and nuclear export of viral ribonucleoprotein complex upon influenza virus infection. PLoS One 2013; 8:e75005 [View Article][PubMed]
    [Google Scholar]
  21. Cho YB, Hong S, Kang KW, Kang JH, Lee SM et al. Selective and ATP-competitive kinesin KIF18A inhibitor suppresses the replication of influenza A virus. J Cell Mol Med 2020; 24:5463–5475 [View Article][PubMed]
    [Google Scholar]
  22. Seo YJ, Jothikumar P, Suthar MS, Zhu C, Grakoui A. Local cellular and cytokine cues in the spleen regulate in situ T Cell receptor affinity, function, and fate of CD8+ T Cells. Immunity 2016; 45:988–998 [View Article][PubMed]
    [Google Scholar]
  23. Brydon EW, Morris SJ, Sweet C. Role of apoptosis and cytokines in influenza virus morbidity. FEMS Microbiol Rev 2005; 29:837–850 [View Article][PubMed]
    [Google Scholar]
  24. Hinshaw VS, Olsen CW, Dybdahl-Sissoko N, Evans D. Apoptosis: a mechanism of cell killing by influenza A and B viruses. J Virol 1994; 68:3667–3673 [View Article][PubMed]
    [Google Scholar]
  25. Quirin K, Eschli B, Scheu I, Poort L, Kartenbeck J et al. Lymphocytic choriomeningitis virus uses a novel endocytic pathway for infectious entry via late endosomes. Virology 2008; 378:21–33 [View Article][PubMed]
    [Google Scholar]
  26. Dong WJ, Wei XL, Zhang FY, Hao JF, Huang F et al. A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways. Sci Rep 2014; 4:7237 [View Article][PubMed]
    [Google Scholar]
  27. Dou D, Revol R, Ostbye H, Wang H, Daniels R. Influenza A virus cell entry, replication, virion assembly and movement. Front Immunol 2018; 9:1581 [View Article][PubMed]
    [Google Scholar]
  28. Yang J, Li M, Shen X, Liu S. Influenza A virus entry inhibitors targeting the hemagglutinin. Viruses 2013; 5:352–373 [View Article][PubMed]
    [Google Scholar]
  29. Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830; 2013:3670–3695
    [Google Scholar]
  30. Sharif Sharifi M, Hazell SL. Fractionation of Mastic gum in relation to antimicrobial activity. Pharmaceuticals 2009; 2:2–10 [View Article][PubMed]
    [Google Scholar]
  31. Papada E, Kaliora AC. Antioxidant and anti-inflammatory properties of Mastiha: a review of preclinical and clinical studies. Antioxidants 2019; 8:E208 [View Article][PubMed]
    [Google Scholar]
  32. Tosh PK, Jacobson RM, Poland GA. Influenza vaccines: from surveillance through production to protection. Mayo Clin Proc 2010; 85:257–273 [View Article][PubMed]
    [Google Scholar]
  33. Nguyen JT, Hoopes JD, Le MH, Smee DF, Patick AK et al. Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains in vitro. PLoS One 2010; 5:e9332 [View Article][PubMed]
    [Google Scholar]
  34. Zaraket H, Saito R, Suzuki Y, Baranovich T, Dapat C et al. Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza A/H1N1 viruses. J Clin Microbiol 2010; 48:1085–1092 [View Article][PubMed]
    [Google Scholar]
  35. Wang R, Zhu Y, Zhao J, Ren C, Li P et al. Autophagy promotes replication of influenza A Virus in vitro . J Virol 2019; 93: [View Article][PubMed]
    [Google Scholar]
  36. Heldt FS, Frensing T, Reichl U. Modeling the intracellular dynamics of influenza virus replication to understand the control of viral RNA synthesis. J Virol 2012; 86:7806–7817 [View Article][PubMed]
    [Google Scholar]
  37. Edinger TO, Pohl MO, Stertz S. Entry of influenza A virus: host factors and antiviral targets. J Gen Virol 2014; 95:263–277 [View Article][PubMed]
    [Google Scholar]
  38. Lou Z, Sun Y, Rao Z. Current progress in antiviral strategies. Trends Pharmacol Sci 2014; 35:86–102 [View Article][PubMed]
    [Google Scholar]
  39. Este JA, Telenti A. HIV entry inhibitors. Lancet 2007; 370:81–88 [View Article][PubMed]
    [Google Scholar]
  40. Briz V, Poveda E, Soriano V. HIV entry inhibitors: mechanisms of action and resistance pathways. J Antimicrob Chemother 2006; 57:619–627 [View Article][PubMed]
    [Google Scholar]
  41. Tilton JC, Doms RW. Entry inhibitors in the treatment of HIV-1 infection. Antiviral Res 2010; 85:91–100 [View Article][PubMed]
    [Google Scholar]
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