Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus

Rubén Soto-Acosta, Patricia Bautista-Carbajal, Gulam H. Syed, Aleem Siddiqui, Rosa M. Del Angel

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome. A DENV replicative cycle relies on host lipid metabolism; specifically, DENV infection modulates cholesterol and fatty acid synthesis, generating a lipid-enriched cellular environment necessary for viral replication. Thus, the aim of this work was to evaluate the anti-DENV effect of the Nordihydroguaiaretic acid (NDGA), a hypolipidemic agent with antioxidant and anti-inflammatory properties. A dose-dependent inhibition in viral yield and NS1 secretion was observed in supernatants of infected cells treated for 24 and 48 h with different concentrations of NDGA. To evaluate the effect of NDGA in DENV replication, a DENV4 replicon transfected Vero cells were treated with different concentrations of NDGA. NDGA treatment significantly reduced DENV replication, reiterating the importance of lipids in viral replication. NDGA treatment also led to reduction in number of lipid droplets (LDs), the neutral lipid storage organelles involved in DENV morphogenesis that are known to increase in number during DENV infection. Furthermore, NDGA treatment resulted in dissociation of the C protein from LDs. Overall our results suggest that NDGA inhibits DENV infection by targeting genome replication and viral assembly.

Original languageEnglish (US)
Pages (from-to)132-140
Number of pages9
JournalAntiviral research
Volume109
Issue number1
DOIs
StatePublished - Sep 2014

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Keywords

  • Antiviral
  • Dengue
  • Morphogenesis
  • Replication

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Soto-Acosta, R., Bautista-Carbajal, P., Syed, G. H., Siddiqui, A., & Del Angel, R. M. (2014). Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus. Antiviral research, 109(1), 132-140. https://doi.org/10.1016/j.antiviral.2014.07.002