title: Genistein, a general kinase inhibitor, as a potential antiviral for arenaviral hemorrhagic fever as described in the Pirital virus-Syrian golden hamster model.
abstract: Arenaviruses are rodent-borne negative strand RNA viruses and infection of these viruses in humans may result in disease and hemorrhagic fever. To date, supportive care, ribavirin, and in some cases immune plasma remain the foremost treatment options for arenaviral hemorrhagic fever. Research with the hemorrhagic fever causing-arenaviruses usually requires a Biosafety level (BSL)-4 environment; however, surrogate animal model systems have been developed to preliminarily study and screen various vaccines and antivirals. The Syrian golden hamster-Pirital virus (PIRV) surrogate model of hemorrhagic fever provides an opportunity to test new antivirals in an ABSL-3 setting. Thus, we challenged hamsters, implanted with telemetry, with PIRV and observed viremia and tissue viral titers, and changes in core body temperature, hematology, clinical chemistry, and coagulation parameters. Physical signs of disease of the PIRV-infected hamsters included weight loss, lethargy, petechial rashes, epistaxis, ocular orbital and rectal hemorrhage, and visible signs of neurologic disorders. However, treating animals with genistein, a plant derived isoflavone and general kinase inhibitor, resulted in increased survival rates and led to an improved clinical profile. In all, the results from this study demonstrate the potential of a general kinase inhibitor genistein as an antiviral against arenaviral hemorrhagic fever.
authors.affiliation: Battelle Memorial Institute, 505 King Avenue, Columbus, OH 43201, USA. velae@battelle.org
authors.forename: Eric M
authors.initials: EM
authors.lastname: Vela
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Knostman
authors.forename: Jason M
authors.initials: JM
authors.lastname: Mott
authors.forename: Richard L
authors.initials: RL
authors.lastname: Warren
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Garver
authors.forename: Lela Johnson
authors.initials: LJ
authors.lastname: Vela
authors.forename: Rachelle L
authors.initials: RL
authors.lastname: Stammen
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D001117:Arenaviridae Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006477:Arenaviruses, New World / Q000302:isolation & purification / Q000472:pathogenicity*; D001774:Blood Chemical Analysis; D001777:Blood Coagulation; D001831:Body Temperature; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D008647:Mesocricetus; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D012720:Severity of Illness Index; D016019:Survival Analysis; D013686:Telemetry; D019562:Viral Load; D014766:Viremia
chemical_list: D000998:Antiviral Agents; D047428:Protein Kinase Inhibitors; D019833:Genistein