Identification of a Small-molecule Antiviral with Broad-spectrum Application to Multiple, Lethal Virus Types

Abstract

We report herein the identification of a small molecule therapeutic, FGI-103, which displays potent and broad spectrum in vitro inhibition of lethal viral hemorrhagic fevers to include Ebola, Rift Valley Fever and Dengue. Using lethal in vivo mouse model of Ebola virus, we further demonstrate that FGI-103 can protect animals froman otherwise lethal infection when used either in a prophylactic or therapeutic setting and that a 'single treatment', administered after infection, is sufficient to confer protection from lethal Ebola or Marburg virus challenge. 100% efficacy from a single, low dose treatment provides a proof-of-concept direct in vivo validation that FGI-103 in its current composition is bioavailable, efficacious and a viable lead for further therapeutic development. Exploratory in vitro antiviral testing further identified inhibitory activity against members of many different, otherwise unrelated virus families to include RSV, PIV and HBV, suggesting that perhaps FGI-103 potentially interferes with a common 'host' - target or - pathway utilized to varying extent by these different viruses. Altogether, these findings suggest FGI-103may provide amuch-needed 'broad-spectrum' opportunity to target multiple and otherwise intractable viral diseases.