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

Research output: Contribution to journalArticle

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 - Sep 1 2018

Fingerprint

Antimalarials
Hepatitis C
Viruses
Hepacivirus
Antiviral Agents
Japanese Encephalitis Virus
Hepatitis E virus
Dengue Virus
Hepatitis B virus
Pharmaceutical Preparations
Flaviviridae
RNA
Flavivirus
Hepatitis Viruses
Viral Proteins

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

Multiple antiviral activities of the antimalarial and anti-hepatitis C drug candidates N-89 and N-251. / Ueda, Youki; Gu, Weilin; Dansako, Hiromichi; Kim, Hye-Sook; Yoshizaki, Sayaka; Okumura, Nobuaki; Ishikawa, Tomohiro; Nishitsuji, Hironori; Kato, Fumihiro; Hishiki, Takayuki; Satoh, Shinya; Ishii, Koji; Masuda, Michiaki; Shimotohno, Kunitada; Ikeda, Masanori; Kato, Nobuyuki.

In: Biochemistry and Biophysics Reports, Vol. 15, 01.09.2018, p. 1-6.

Research output: Contribution to journalArticle

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, vol. 15, pp. 1-6. https://doi.org/10.1016/j.bbrep.2018.05.007
Ueda, Youki ; Gu, Weilin ; Dansako, Hiromichi ; Kim, Hye-Sook ; Yoshizaki, Sayaka ; Okumura, Nobuaki ; Ishikawa, Tomohiro ; Nishitsuji, Hironori ; Kato, Fumihiro ; Hishiki, Takayuki ; Satoh, Shinya ; Ishii, Koji ; Masuda, Michiaki ; Shimotohno, Kunitada ; Ikeda, Masanori ; Kato, Nobuyuki. / Multiple antiviral activities of the antimalarial and anti-hepatitis C drug candidates N-89 and N-251. In: Biochemistry and Biophysics Reports. 2018 ; Vol. 15. pp. 1-6.
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