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
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Antiviral and immunomodulatory effects of ouabain against Congenital Zika Syndrome model.
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/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 TNF and IL-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 further investigated as a promising treatment for CZS.
期刊介绍:
Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.