Nuclear import inhibitor N-(4-hydroxyphenyl) retinamide targets Zika virus (ZIKV) nonstructural protein 5 to inhibit ZIKV infection

Chunxiao Wang, Sundy N.Y. Yang, Kate Smith, Jade K. Forwood, David A. Jans

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Abstract

In the absence of approved therapeutics, Zika virus (ZIKV)'s recent prolific outbreaks in the Americas, together with impacts on unborn fetuses of infected mothers, make it a pressing human health concern worldwide. Although a key player in viral replication in the infected host cell cytoplasm, ZIKV non-structural protein 5 (NS5) appears to contribute integrally to pathogenesis by localising in the host cell nucleus, in similar fashion to NS5 from Dengue virus (DENV). We show here for the first time that ZIKV NS5 is recognized with high nanomolar affinity by the host cell importin α/β1 heterodimer, and that this interaction can be blocked by the novel DENV NS5 targeting inhibitor N-(4-hydroxyphenyl) retinamide (4-HPR). Importantly, we show that 4-HPR has potent anti-ZIKV activity at low μM concentrations. With an established safety profile for human use, 4-HPR represents an exciting possibility as an anti-ZIKV agent.

Original languageEnglish
Pages (from-to)1555-1559
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume493
Issue number4
DOIs
Publication statusPublished - 2 Dec 2017

Keywords

  • Flavivirus
  • Importins
  • Nuclear transport inhibitors
  • Viral infection
  • Zika virus

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