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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2 Citations (Scopus)

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 - 09-2018

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

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    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