Advertisement

Journal of Microbiology

, Volume 57, Issue 1, pp 74–79 | Cite as

Anti-varicella-zoster virus activity of cephalotaxine esters in vitro

  • Jung-Eun Kim
  • Yoon-Jae SongEmail author
Virology
  • 37 Downloads

Abstract

Harringtonine (HT) and homoharringtonine (HHT), alkaloid esters isolated from the genus Cephalotaxus, exhibit antitumor activity. A semisynthetic HHT has been approved for treatment of chronic myelogenous leukemia. In addition to antileukemic activity, HT and HHT are reported to possess potent antiviral activity. In this study, we investigated the effects of HT and HHT on replication of varicella-zoster virus (VZV) in vitro. HT and HHT, but not their biologically inactive parental alkaloid cephalotaxine (CET), significantly inhibited replication of recombinant VZV-pOka luciferase. Furthermore, HT and HHT, but not CET, strongly induced down-regulation of VZV lytic genes and exerted potent antiviral effects against a VZV clinical isolate. The collective data support the utility of HT and HHT as effective antiviral candidates for treatment of VZV-associated diseases.

Keywords

varicella zoster virus antiviral harringtonine homoharringtonine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arvin, A.M. 1996. Varicella-zoster virus. Clin. Microbiol. Rev. 9, 361–381.CrossRefGoogle Scholar
  2. Arvin, A.M. 2002. Antiviral therapy for varicella and herpes zoster. Semin. Pediatr. Infect. Dis. 13, 12–21.CrossRefGoogle Scholar
  3. Arvin, A. and Gilden, D. 2013. Varicella-zoster virus, pp. 2015–2057. In Knipe, D.M. and Howley, P.M. (eds.), Fields virology, Philadelphia (Pennsylvania): Lippincott Williams & Wilkins.Google Scholar
  4. Bae, S., Kim, S.Y., Do, M.H., Lee, C.H., and Song, Y.J. 2017. 1,2,3,4,6-penta-O-galloyl-ß-D-glucose, a bioactive compound in Elaeocarpus sylvestris extract, inhibits varicella-zoster virus replication. Antiviral Res. 144, 266–272.CrossRefGoogle Scholar
  5. Bae, S. and Song, Y.J. 2017. Inhibition of varicellazoster virus replication by an ethanol extract of Lysimachia mauritiana. Mol. Med. Rep. 15, 3847–3851.CrossRefGoogle Scholar
  6. Cao, J., Forrest, J.C., and Zhang, X. 2015. A screen of the NIH clinical collection small molecule library identifies potential anticoronavirus drugs. Antiviral Res. 114, 1–10.CrossRefGoogle Scholar
  7. Chen, R., Guo, L., Chen, Y., Jiang, Y., Wierda, W.G., and Plunkett, W. 2011. Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia. Blood 117, 156–164.CrossRefGoogle Scholar
  8. Cohen, J.I., Brunell, P.A., Straus, S.E., and Krause, P.R. 1999. Recent advances in varicella-zoster virus infection. Ann. Intern. Med. 130, 922–932.CrossRefGoogle Scholar
  9. Fresno, M., Jimenez, A., and Vazquez, D. 1977. Inhibition of translation in eukaryotic systems by harringtonine. Eur. J. Biochem. 72, 323–330.CrossRefGoogle Scholar
  10. Gnann Jr, J.W. 2007. Antiviral therapy of varicella-zoster virus infections. In Arvin, A., Campadelli-Fiume, G., Mocarski, E., Moore, P.S., Roizman, B., Whitley, R., and Yamanishi, K. (eds.), Human herpesviruses: Biology, therapy, and immunoprophylaxis, Cambridge, UK.CrossRefGoogle Scholar
  11. Huang, M.T. 1975. Harringtonine, an inhibitor of initiation of protein biosynthesis. Mol. Pharmacol. 11, 511–519.Google Scholar
  12. Ida, M., Kageyama, S., Sato, H., Kamiyama, T., Yamamura, J., Kurokawa, M., Morohashi, M., and Shiraki, K. 1999. Emergence of resistance to acyclovir and penciclovir in varicella-zoster virus and genetic analysis of acyclovir-resistant variants. Antiviral Res. 40, 155–166.CrossRefGoogle Scholar
  13. Jeon, J.S., Won, Y.H., Kim, I.K., Ahn, J.H., Shin, O.S., Kim, J.H., and Lee, C.H. 2016. Analysis of single nucleotide polymorphism among varicella-zoster virus and identification of vaccine-specific sites. Virology 496, 277–286.CrossRefGoogle Scholar
  14. Jia, K., Yuan, Y., Liu, W., Liu, L., Qin, Q., and Yi, M. 2018. Identification of inhibitory compounds against Singapore grouper iridovirus infection by cell viability-based screening assay and droplet digital PCR. Mar. Biotechnol. (NY) 20, 35–44.CrossRefGoogle Scholar
  15. Kaur, P., Thiruchelvan, M., Lee, R.C., Chen, H., Chen, K.C., Ng, M.L., and Chu, J.J. 2013. Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob. Agents Chemother. 57, 155–167.CrossRefGoogle Scholar
  16. Kim, J.E., Kim, S.Y., Lim, S.Y., Kieff, E., and Song, Y.J. 2014. Role of Ca2+/calmodulin-dependent kinase II-IRAK1 interaction in LMP1-induced NF-kappaB activation. Mol. Cell. Biol. 34, 325–334.CrossRefGoogle Scholar
  17. Lu, S. and Wang, J. 2014. Homoharringtonine and omacetaxine for myeloid hematological malignancies. J. Hematol. Oncol. 7, 2.CrossRefGoogle Scholar
  18. Morfin, F., Thouvenot, D., De Turenne-Tessier, M., Lina, B., Aymard, M., and Ooka, T. 1999. Phenotypic and genetic characterization of thymidine kinase from clinical strains of varicellazoster virus resistant to acyclovir. Antimicrob. Agents Chemother. 43, 2412–2416.CrossRefGoogle Scholar
  19. Powell, R.G., Weisleder, D., and Smith Jr, C.R. 1972. Antitumor alkaloids for Cephalataxus harringtonia: Structure and activity. J. Pharm. Sci. 61, 1227–1230.CrossRefGoogle Scholar
  20. Quintas-Cardama, A., Kantarjian, H., and Cortes, J. 2009. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa2009. Cancer 115, 5382–5393.CrossRefGoogle Scholar
  21. Romero, M.R., Serrano, M.A., Efferth, T., Alvarez, M., and Marin, J.J. 2007. Effect of cantharidin, cephalotaxine and homoharringtonine on “in vitro” models of hepatitis B virus (HBV) and bovine viral diarrhoea virus (BVDV) replication. Planta Med. 73, 552–558.CrossRefGoogle Scholar
  22. Tujebajeva, R.M., Graifer, D.M., Matasova, N.B., Fedorova, O.S., Odintsov, V.B., Ajtkhozhina, N.A., and Karpova, G.G. 1992. Selective inhibition of the polypeptide chain elongation in eukaryotic cells. Biochim. Biophys. Acta 1129, 177–182.CrossRefGoogle Scholar
  23. Zhang, Z., Rowe, J., Wang, W., Sommer, M., Arvin, A., Moffat, J., and Zhu, H. 2007. Genetic analysis of varicella-zoster virus ORF0 to ORF4 by use of a novel luciferase bacterial artificial chromosome system. J. Virol. 81, 9024–9033.CrossRefGoogle Scholar
  24. Zhou, D.C., Zittoun, R., and Marie, J.P. 1995. Homoharringtonine: An effective new natural product in cancer chemotherapy. Bull. Cancer 82, 987–995.Google Scholar

Copyright information

© The Microbiological Society of Korea and Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Life ScienceGachon UniversitySeongnamRepublic of Korea

Personalised recommendations