Inhibition of Na+/K+ ATPase blocks Zika virus infection in mice.

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.

• Authors: Jiao Guo, Xiaoying Jia, Yang Liu, Shaobo Wang, Junyuan Cao, Bo Zhang, Gengfu Xiao, Wei Wang
• Journal: Communications biology (Commun Biol) Vol. 3 Issue 1 Pg. 380 (07 15 2020) ISSN: 2399-3642 [Electronic] England
• PMID: 32669655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Ouabain
• Digoxin
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Antiviral Agents (therapeutic use)
• Brain (virology)
• Digoxin (therapeutic use)
• Female
• Fetal Diseases (prevention & control, virology)
• Infectious Disease Transmission, Vertical (prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Ouabain (therapeutic use)
• Pregnancy
• Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors, metabolism)
• Viral Load (drug effects)
• Zika Virus Infection (prevention & control)