Drug Screening for Hepatitis A Virus (HAV): Nicotinamide Inhibits c-Jun Expression and HAV Replication

Reina Sasaki-Tanaka, Ryota Masuzaki, Hiroaki Okamoto, Toshikatsu Shibata, Mitsuhiko Moriyama, Hirofumi Kogure, Tatsuo Kanda

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Hepatitis A virus (HAV) infection often causes acute hepatitis, which results in a case fatality rate of 0.2% and fulminant hepatitis in 0.5% of cases. However, no specific potent anti-HAV drug is available on the market to date. In the present study, we focused on inhibition of HAV internal ribosomal entry site (IRES)-mediated translation and investigated novel therapeutic drugs through drug repurposing by screening for inhibitors of HAV IRES-mediated translation and cell viability using a reporter assay and cell viability assay, respectively. The initial screening of 1,158 drugs resulted in 77 candidate drugs. Among them, nicotinamide significantly inhibited HAV HA11-1299 genotype IIIA replication in Huh7 cells. This promising drug also inhibited HAV HM175 genotype IB subgenomic replicon and HAV HA11-1299 genotype IIIA replication in a dose-dependent manner. In the present study, we found that nicotinamide inhibited the activation of activator protein 1 (AP-1) and that knockdown of c-Jun, which is one of the components of AP-1, inhibited HAV HM175 genotype IB IRES-mediated translation and HAV HA11-1299 genotype IIIA and HAV HM175 genotype IB replication. Taken together, the results showed that nicotinamide inhibited c-Jun, resulting in the suppression of HAV IRES-mediated translation and HAV replication, and therefore, it could be useful for the treatment of HAV infection.

Original languageEnglish
JournalJournal of Virology
Volume97
Issue number2
DOIs
Publication statusPublished - Feb 2023

Keywords

  • AP-1
  • IRES
  • c-Jun
  • hepatitis A virus
  • internal ribosome entry site
  • nicotinamide

Fingerprint

Dive into the research topics of 'Drug Screening for Hepatitis A Virus (HAV): Nicotinamide Inhibits c-Jun Expression and HAV Replication'. Together they form a unique fingerprint.

Cite this