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

doi:10.1016/j.ymthe.2024.12.021

Antiviral and immunomodulatory effects of ouabain against congenital Zika syndrome model

Mol Ther. 2024 Dec 14:S1525-0016(24)00820-7. doi: 10.1016/j.ymthe.2024.12.021. Online ahead of print.

Affiliations

¹ Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba (UFPB), João Pessoa 58051-900, Paraiba, Brazil; Department of Virology, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife 50740-465, Pernambuco, Brazil; Department of Neurobiology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
² Department of Neurobiology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
³ Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
⁴ Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba (UFPB), João Pessoa 58051-900, Paraiba, Brazil; Medical Sciences and Nursing Complex, Federal University of Alagoas, Arapiraca, 57309-005, Brazil.
⁵ Department of Virology, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife 50740-465, Pernambuco, Brazil.
⁶ Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba (UFPB), João Pessoa 58051-900, Paraiba, Brazil.
⁷ Department of Neurobiology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA. Electronic address: [email protected].
⁸ Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA. Electronic address: [email protected].

PMID: 39674887
DOI: 10.1016/j.ymthe.2024.12.021

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.

Keywords: Zika virus; arbovirus; cardiotonic steroid; congenital zika syndrome; inflammation; neural stem cells.