Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid

  • Hung H
  • Chen T
  • Fang M
 et al. 
  • 22

    Readers

    Mendeley users who have this article in their library.
  • 37

    Citations

    Citations of this article.

Abstract

OBJECTIVES: Enterovirus 71 (EV71) causes serious diseases in humans. The aim of this study was to examine the effects of aurintricarboxylic acid (ATA) on EV71 replication and to explore the underlying mechanism.

METHODS: To measure the activity of ATA in inhibiting the cytopathic effect (CPE) of EV71, a cell-based neutralization (inhibition of virus-induced CPE) assay was performed. The effect of ATA was further confirmed using plaque reduction and viral yield reduction assays. A time of addition assay was performed to identify the mechanisms of ATA's anti-EV71 activity. We examined the effects of ATA on the following key steps involved in virus replication: (i) translation of the internal ribosomal entry site (IRES)-mediated viral polyprotein; (ii) the proteolytic activity of viral proteases 2A and/or 3C; and (iii) the viral 3D RNA-dependent RNA polymerase (RdRp) activity.

RESULTS: In this study, ATA was found to be a potent inhibitor of the replication of EV71. In the antiviral neutralization assay, ATA exhibited inhibitory activity against EV71 (TW/4643/98) and EV71 (TW/2231/98). Plaque assay further demonstrated that ATA inhibited EV71 replication with an EC(50) (effective concentration at which 50% of plaques were removed) of 2.9 microM. Studies on the mechanism of action revealed that ATA targets the early stage of the viral life cycle after viral entry. ATA was able to inhibit the RdRp activity of EV71, while neither the IRES-mediated translation of viral polyprotein nor the viral 3C protease activity was affected.

CONCLUSIONS: Overall, the findings in this study suggest that ATA is able to effectively inhibit EV71 replication through interfering with the viral 3D polymerase.

Author-supplied keywords

  • Enteroviruses
  • Polyanionic compounds
  • RNA-dependent RNA polymerase

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Hui Chen Hung

  • Tzu Chun Chen

  • Ming Yu Fang

  • Kuei Jung Yen

  • Shin Ru Shih

  • John T A Hsu

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free