title: The Viral Polymerase Inhibitor 7-Deaza-2'-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model.
abstract: Zika virus (ZIKV) is an emerging flavivirus typically causing a dengue-like febrile illness, but neurological complications, such as microcephaly in newborns, have potentially been linked to this viral infection. We established a panel of in vitro assays to allow the identification of ZIKV inhibitors and demonstrate that the viral polymerase inhibitor 7-deaza-2'-C-methyladenosine (7DMA) efficiently inhibits replication. Infection of AG129 (IFN-α/β and IFN-γ receptor knock-out) mice with ZIKV resulted in acute neutrophilic encephalitis with viral antigens accumulating in neurons of the brain and spinal cord. Additionally, high levels of viral RNA were detected in the spleen, liver and kidney, and levels of IFN-γ and IL-18 were systematically increased in serum of ZIKV-infected mice. Interestingly, the virus was also detected in testicles of infected mice. In line with its in vitro anti-ZIKV activity, 7DMA reduced viremia and delayed virus-induced morbidity and mortality in infected mice, which also validates this small animal model to assess the in vivo efficacy of novel ZIKV inhibitors. Since AG129 mice can generate an antibody response, and have been used in dengue vaccine studies, the model can also be used to assess the efficacy of ZIKV vaccines.  .
authors.affiliation: Laboratory of Virology and Chemotherapy, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Joanna
authors.initials: J
authors.lastname: Zmurko
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Marques
authors.affiliation: Laboratory of Virology and Chemotherapy, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.affiliation: Department of Pathology, University of Leuven and Leuven University Hospitals, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.affiliation: Laboratory of Virology and Chemotherapy, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Suzanne J F
authors.initials: SJ
authors.lastname: Kaptein
authors.affiliation: Laboratory of Virology and Chemotherapy, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D014372:Tubercidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*; D000071244:Zika Virus / Q000187:drug effects* / Q000502:physiology; D000071243:Zika Virus Infection / Q000188:drug therapy*
chemical_list: D000998:Antiviral Agents; D014372:Tubercidin; C518645:7-deaza-2'-C-methyladenosine