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

Hui Chen Hung, Tzu Chun Chen, Ming Yu Fang, Kuei Jung Yen, Shin Ru Shih, John T.A. Hsu, Ching-Ping Tseng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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 μM. 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.

Original languageEnglish
Article numberdkp502
Pages (from-to)676-683
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume65
Issue number4
DOIs
StatePublished - 20 Jan 2010

Keywords

  • Enteroviruses
  • Polyanionic compounds
  • RNA-dependent RNA polymerase

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