title: Development of a broad-spectrum antiviral with activity against Ebola virus.
abstract: We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.
authors.affiliation: United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. mkinch@functional-genetics.com
authors.forename: M Javad
authors.initials: MJ
authors.lastname: Aman
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kinch
authors.forename: Kelly
authors.initials: K
authors.lastname: Warfield
authors.forename: Travis
authors.initials: T
authors.lastname: Warren
authors.forename: Abdul
authors.initials: A
authors.lastname: Yunus
authors.forename: Sven
authors.initials: S
authors.lastname: Enterlein
authors.forename: Eric
authors.initials: E
authors.lastname: Stavale
authors.forename: Peifang
authors.initials: P
authors.lastname: Wang
authors.forename: Shaojing
authors.initials: S
authors.lastname: Chang
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tang
authors.forename: Kevin
authors.initials: K
authors.lastname: Porter
authors.forename: Michael
authors.initials: M
authors.lastname: Goldblatt
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018890:Chemoprevention; D003716:Dengue Virus / Q000187:drug effects; D029043:Ebolavirus / Q000187:drug effects*; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D012296:Rift Valley fever virus / Q000187:drug effects; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents