Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and Its Associated Congenital Microcephaly in Mice

EBioMedicine. 2017 Oct;24:189-194. doi: 10.1016/j.ebiom.2017.09.034. Epub 2017 Sep 28.

Abstract

Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public.

Keywords: Antiviral effects; Chloroquine; FDA-approved drug; Microcephaly; ZIKV entry.

MeSH terms

  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Chloroquine / administration & dosage*
  • Chloroquine / pharmacology
  • Disease Models, Animal
  • Drug Approval
  • Drug Evaluation, Preclinical
  • Humans
  • Mice
  • Microcephaly / mortality
  • Microcephaly / prevention & control*
  • Microcephaly / virology
  • Vero Cells
  • Virus Internalization / drug effects
  • Zika Virus / drug effects
  • Zika Virus / physiology
  • Zika Virus Infection / complications
  • Zika Virus Infection / drug therapy*
  • Zika Virus Infection / mortality

Substances

  • Chloroquine