Antiviral and immunomodulatory effects of ouabain against congenital Zika syndrome model

Deyse Cristina Madruga Carvalho, Tiffany Dunn, Rafael Kroon Campos, Jessica A. Tierney, Florence Onyoni, Luiz Henrique Agra Cavalcante-Silva, Lindomar José Pena, Sandra Rodrigues-Mascarenhas, Ping Wu, Scott C. Weaver

Research output: Contribution to journalArticlepeer-review

Abstract

Zika virus (ZIKV) is an arbovirus associated with neurological disorders accompanying congenital infections. With no vaccine or antiviral approved, there is an urgent need for the development of effective antiviral agents against ZIKV infection. We evaluated the anti-ZIKV and immunomodulatory activity of ouabain, a Na+/K+-ATPase inhibitor known to have immunomodulatory and antiviral activities, using human neural stem and progenitor cells (hNS/PCs) and a murine model of congenital Zika syndrome (CZS). Our data demonstrated that ouabain reduces ZIKV infection in hNS/PCs, mouse placenta, yolk sac, and the fetal head. Ouabain mitigated neurogenesis impairment triggered by ZIKV in hNS/PCs and prevented ZIKV-mediated reduction of fetus and head sizes. In addition, ouabain decreased tumor necrosis factor and interleukin-1β levels in the placenta, highlighting its immunomodulatory activity in the murine model. Our findings indicate that ouabain possesses anti-ZIKV and immunomodulatory activities, suggesting that it should be investigated further as a promising treatment for CZS.

Original languageEnglish (US)
JournalMolecular Therapy
DOIs
StateAccepted/In press - 2025

Keywords

  • arbovirus
  • cardiotonic steroid
  • congenital zika syndrome
  • inflammation
  • neural stem cells
  • Zika virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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