Multiple antiviral activities of the antimalarial and anti-hepatitis C drug candidates N-89 and N-251

Youki Ueda, Weilin Gu, Hiromichi Dansako, Hye-Sook Kim, Sayaka Yoshizaki, Nobuaki Okumura, Tomohiro Ishikawa, Hironori Nishitsuji, Fumihiro Kato, Takayuki Hishiki, Shinya Satoh, Koji Ishii, Michiaki Masuda, Kunitada Shimotohno, Masanori Ikeda, Nobuyuki Kato

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Abstract

The chemically synthesized endoperoxide compound N-89 and its derivative N-251 were shown to have potent antimalarial activity. We previously demonstrated that N-89 and N-251 potently inhibited the RNA replication of hepatitis C virus (HCV), which belongs to the Flaviviridae family. Since antimalarial and anti-HCV mechanisms have not been clarified, we were interested whether N-89 and N-251 possessed the activity against viruses other than HCV. In this study, we examined the effects of N-89 and N-251 on other flaviviruses (dengue virus and Japanese encephalitis virus) and hepatitis viruses (hepatitis B virus and hepatitis E virus). Our findings revealed that N-89 and N-251 moderately inhibited the RNA replication of Japanese encephalitis virus and hepatitis E virus, although we could not detect those anti-dengue virus activities. We also observed that N-89 and N-251 moderately inhibited the replication of hepatitis B virus at the step after viral translation. These results suggest the possibility that N-89 and N-251 act on some common host factor(s) that are necessary for viral replications, rather than the possibility that N-89 and N-251 directly act on the viral proteins except for HCV. We describe a new type of antiviral reagents, N-89 and N-251, which are applicable to multiple different viruses.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalBiochemistry and Biophysics Reports
Volume15
DOIs
Publication statusPublished - Sep 1 2018

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Keywords

  • Hepatitis B virus
  • Hepatitis E virus
  • Japanese encephalitis virus
  • Multiple antiviral activities
  • N-251
  • N-89

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ueda, Y., Gu, W., Dansako, H., Kim, H-S., Yoshizaki, S., Okumura, N., Ishikawa, T., Nishitsuji, H., Kato, F., Hishiki, T., Satoh, S., Ishii, K., Masuda, M., Shimotohno, K., Ikeda, M., & Kato, N. (2018). Multiple antiviral activities of the antimalarial and anti-hepatitis C drug candidates N-89 and N-251. Biochemistry and Biophysics Reports, 15, 1-6. https://doi.org/10.1016/j.bbrep.2018.05.007