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  • 2 -Fluoro-2 -deoxycytidine is a broad-spectrum inhibitor of bunyaviruses in vitro and in phleboviral disease mouse models #MMPMID30339848
  • Smee DF; Jung KH; Westover J; Gowen BB
  • Antiviral Res 2018[Dec]; 160 (ä): 48-54 PMID30339848garesp_yesshow ga
  • 2'-Fluoro-2'-deoxycytidine (2'-FdC) was reported to inhibit various viruses in vitro, including Borna disease, hepatitis C, Lassa fever, influenza and certain herpes viruses, and is inhibitory to influenza viruses in mice. We investigated the antiviral activity of 2'-FdC against several unrelated bunyaviruses in 50% cytopathic effect (CPE) inhibition assays and, with viruses that cause limited CPE, 90% virus yield reduction (VYR) assays. La Crosse (LACV), Maporal, Punta Toro, Rift Valley fever (RVFV), and San Angelo viruses were inhibited in CPE assays at 2.2-9.7muM concentrations. In VYR assays, Heartland and severe fever with thrombocytopenia syndrome (SFTSV) viruses were inhibited at 0.9 and 3.7muM, respectively. In contrast, ribavirin inhibited these viruses at an average of 47muM. Antiviral efficacy studies were also conducted in mice infected with RVFV, SFTSV, and LACV. Against RVFV, 2'-FdC (100 and 200mg/kg/day) and ribavirin (100mg/kg/day) treatments each delayed mortality by approximately 6 days compared to placebo. Liver, spleen, and serum viral titers were significantly reduced by antiviral treatments. 2'-FdC (100 and 200mg/kg/day) prevented death in SFTSV-infected mice, but was not as effective as favipiravir (100mg/kg/day) based on body weight loss during infection. The 100mg/kg/day doses of 2'-FdC and favipiravir significantly reduced liver, spleen, and serum viral titers. 2'-FdC and ribavirin afforded no protection against LACV infection in mice, which is encephalitic and thus inherently more difficult to treat. Taken together, our data suggest that 2'-FdC may be a viable candidate for treating certain non-encephalitic bunyavirus infections such as those caused by phleboviruses.
  • |Animal Structures/virology[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*administration & dosage/*pharmacology[MESH]
  • |Body Weight[MESH]
  • |Bunyaviridae Infections/*drug therapy[MESH]
  • |Cytopathogenic Effect, Viral[MESH]
  • |DNA Viruses/*drug effects/growth & development[MESH]
  • |Deoxycytidine/administration & dosage/*analogs & derivatives/pharmacology[MESH]
  • |Disease Models, Animal[MESH]
  • |Mice[MESH]
  • |Microbial Sensitivity Tests[MESH]
  • |Placebos/administration & dosage[MESH]
  • |RNA Viruses/*drug effects/growth & development[MESH]
  • |Survival Analysis[MESH]
  • |Treatment Outcome[MESH]
  • |Viral Load[MESH]

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    48 ä.160 2018