title: Broad-spectrum inhibitor of viruses in the Flaviviridae family.
abstract: The viruses in the Flaviviridae family have been associated with human and animal diseases. In this report, we demonstrate that compound 2-amino-8-(beta-D-ribofuranosyl) imidazo [1,2-a]-s-triazine-4-one (ZX-2401) was capable of inhibiting the production in culture of at least five members of the Flaviviridae family with minimal cytotoxicity. This compound inhibited yellow fever virus, dengue virus, bovine viral diarrhea virus, banzi virus and West Nile virus with EC50 of 10, 10, 5, 5 and 3 microg/ml, respectively, and the CC50 in these experiments were greater than 1000 microg/ml. The activity of ZX-2401 is comparable to or better than the control drugs in these studies and was not affected by MOI variation. In addition, ZX-2401 inhibited HCV replication in a dose response fashion in the replicon assay system. Furthermore, ZX-2401 exhibited a synergistic antiviral activity in combination with IFN in tissue culture. The data described herein suggest that ZX-2401 is a broad-spectrum inhibitor of the RNA viruses, which has merit for development of treatments for the emerging infections caused by the viruses in the Flaviviridae family.
authors.affiliation: ZymeTx Inc., 655 Research Parkway, Suite 554; Oklahoma City, OK 73104, USA. Ojwangj@zymetx.com
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Ojwang
authors.forename: Shoukath
authors.initials: S
authors.lastname: Ali
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smee
authors.forename: John D
authors.initials: JD
authors.lastname: Morrey
authors.forename: Craig D
authors.initials: CD
authors.lastname: Shimasaki
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sidwell
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D003716:Dengue Virus / Q000187:drug effects; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects; D018067:Flaviviridae / Q000187:drug effects*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D009499:Neutral Red; D014779:Virus Replication / Q000187:drug effects; D014902:West Nile virus / Q000187:drug effects; D015005:Yellow fever virus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006151:Guanosine; D009499:Neutral Red; C035861:2-amino-8-(beta-ribofuranosyl)imidazo(1,2-a)-1,3,5-triazin-4-one