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

• DOI: 10.1038/s42003-020-1109-8
• Publication Date: 2020-07-15T10:04:02Z
• Authors: Jiao Guo; Xiaoying Jia; Yang Liu; Shaobo Wang; Junyuan Cao; Bo Zhang; Gengfu Xiao; Wei Wang
• Keywords: Male; 0301 basic medicine; Digoxin; Zika Virus Infection; Brain; Viral Load; Antiviral Agents; Article; Infectious Disease Transmission, Vertical; 3. Good health; Mice, Inbred C57BL; Fetal Diseases; Mice; 03 medical and health sciences; Pregnancy; Animals; Female; Sodium-Potassium-Exchanging ATPase; Ouabain

AbstractZika 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.