Abstract
Zika virus (ZIKV) is an infectious disease that has become an important concern worldwide, it associates with neurological disorders and congenital malformations in adults, also leading to fetal intrauterine growth restriction and microcephaly during pregnancy. However, there are currently no approved vaccines or specific antiviral drugs for preventing or treating ZIKV infection. Here, we show that two FDA-approved Na+/K+-ATPase inhibitors, ouabain and digoxin, can block ZIKV infection at the replication stage by targeting Na+/K+-ATPase. Furthermore, ouabain reduced the viral burden of ZIKV in adult mice, penetrated the placental barrier to enter fetal tissues, and protected fetal mice from ZIKV infection-induced microcephaly in a pregnant mouse model. Thus, ouabain has therapeutic potential for ZIKV.
Highlights
Zika virus (ZIKV) is an infectious disease that has become an important concern worldwide, it associates with neurological disorders and congenital malformations in adults, leading to fetal intrauterine growth restriction and microcephaly during pregnancy
To verify the antiviral effects of ouabain and digoxin, we investigated their effects on different ZIKV strains using various cell types
Our results confirm that ouabain and digoxin inhibited ZIKV infection in a dosedependent manner in vitro
Summary
Zika virus (ZIKV) is an infectious disease that has become an important concern worldwide, it associates with neurological disorders and congenital malformations in adults, leading to fetal intrauterine growth restriction and microcephaly during pregnancy. To verify the antiviral effects of ouabain and digoxin, we investigated their effects on different ZIKV strains using various cell types. Consistent with this inhibition, expression of the viral structural protein NS3 was hardly detectable following treatment with the indicated concentration of digoxin or ouabain (Fig. 1i, j).
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