Discovery of Drug Candidates that Inhibit and Eliminate Zika Virus Infection

Technology Overview

ZIKV, a mosquito-borne positive-sense single-stranded RNA virus, infects fetal and adult human brains, and is associated with serious neurological complications including microcephaly and Guillain-Barr̩ Syndrome (GBS). To date, no prophylactic or therapeutic treatment is available to prevent or treat ZIKV infection.

The inventors performed a high content chemical screen using a library containing FDA-approved drugs or drug candidates. Two compounds, hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) were discovered to inhibit ZIKV infection in human cortical neuron progenitor cells (hNPCs).

HH was further validated to inhibit ZIKV infection and to rescue ZIKV-induced growth and differentiation defects in human fetal-like forebrain organoids, while preserving normal neural architecture. HH and AQ also suppressed ZIKV infection in adult mouse brain in vivo. Strikingly, HH and AQ fully rescued the severe limb paralysis syndrome developed in ZIKV infected adult mice. This study identifies drug candidates for treatment of ZIKV infection and ZIKV-related neurological complications in fetal and adult patients.

Potential Applications

• This invention identifies drug candidates that provide long-term in vivo control of ZIKV infection in both fetal and adult brain.
• This invention can be used to develop broadly effective clinical therapies for ZIKV infection.