Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen

In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of ∼6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds; we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and three-dimensional organoid cultures. Ten structurally unrelated inhibitors of cyclin-dependent kinases…

• BA
  Brain and Behavior Research Foundation
• SF
  Simons Foundation

  Award: 308988
• NY
  New York Stem Cell Foundation
• FS
  Florida State University
• EU
  Emory University
• MS
  Maryland Stem Cell Research Fund

  Awards: NS095348, MH105128, NS048271
• SF
  Simons Foundation Autism Research Initiative
• NI
  National Institutes of Health

  Awards: MH106056, AG005138, AI119530, MH101454, MH106434, NS047344, NS095348, NS048271, NS097206, AG046170
• NC
  National Center for Advancing Translational Sciences