In light of the current outbreak of
Ebola virus disease, there is an urgent need to develop effective
therapeutics to treat
Ebola infection, and
drug repurposing screening is a potentially rapid approach for identifying such
therapeutics. We developed a biosafety level 2 (BSL-2) 1536-well plate assay to screen for entry inhibitors of Ebola virus-like particles (VLPs) containing the
glycoprotein (GP) and the matrix VP40
protein fused to a
beta-lactamase reporter
protein and applied this assay for a rapid
drug repurposing screen of Food and Drug Administration (FDA)-approved drugs. We report here the identification of 53 drugs with activity of blocking Ebola VLP entry into cells. These 53 active compounds can be divided into categories including microtubule inhibitors,
estrogen receptor modulators,
antihistamines,
antipsychotics, pump/channel antagonists, and anticancer/
antibiotics. Several of these compounds, including microtubule inhibitors and
estrogen receptor modulators, had previously been reported to be active in BSL-4 infectious Ebola virus replication assays and in animal model studies. Our assay represents a robust, effective and rapid high-throughput screen for the identification of lead compounds in
drug development for the treatment of
Ebola virus infection.