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10.1016/j.antiviral.2011.09.001

http://scihub22266oqcxt.onion/10.1016/j.antiviral.2011.09.001
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suck abstract from ncbi


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pmid21925541      Antiviral+Res 2011 ; 92 (2): 329-40
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  • In vitro and in vivo efficacy of fluorodeoxycytidine analogs against highly pathogenic avian influenza H5N1, seasonal, and pandemic H1N1 virus infections #MMPMID21925541
  • Kumaki Y; Day CW; Smee DF; Morrey JD; Barnard DL
  • Antiviral Res 2011[Nov]; 92 (2): 329-40 PMID21925541show ga
  • Various fluorodeoxyribonucleosides were evaluated for their antiviral activities against influenza virus infections in vitro and in vivo. Among the most potent inhibitors was 2'-deoxy-2'-fluorocytidine (2'-FdC). It inhibited various strains of low and highly pathogenic avian influenza H5N1 viruses, pandemic H1N1 viruses, an oseltamivir-resistant pandemic H1N1 virus, and seasonal influenza viruses (H3N2, H1N1, influenza B) in MDCK cells, with the 90% inhibitory concentrations ranging from 0.13 to 4.6 muM, as determined by a virus yield reduction assay. 2'-FdC was then tested for efficacy in BALB/c mice infected with a lethal dose of highly pathogenic influenza A/Vietnam/1203/2004 H5N1 virus. 2'FdC (60 mg/kg/d) administered intraperitoneally (i.p.) twice a day beginning 24 h after virus exposure significantly promoted survival (80% survival) of infected mice (p=0.0001). Equally efficacious were the treatment regimens in which mice were treated with 2'-FdC at 30 or 60 mg/kg/day (bid X 8) beginning 24 h before virus exposure. At these doses, 70-80% of the mice were protected from death due to virus infection (p=0.0005, p=0.0001; respectively). The lungs harvested from treated mice at day four of the infection displayed little surface pathology or histopathology, lung weights were lower, and the 60 mg/kg dose reduced lung virus titers, although not significantly compared to the placebo controls. All doses were well tolerated in uninfected mice. 2'-FdC could also be administered as late as 72 h post virus exposure and still significantly protect 60% mice from the lethal effects of the H5N1 virus infection (p=0.019). Other fluorodeoxyribonucleosides tested in the H5N1 mouse model, 2'-deoxy-5-fluorocytidine and 2'-deoxy-2',2'-difluorocytidine, were very toxic at higher doses and not inhibitory at lower doses. Finally, 2'-FdC, which was active in the H5N1 mouse model, was also active in a pandemic H1N1 influenza A infection model in mice. When given at 30 mg/kg/d (bid X 5) beginning 24h before virus exposure), 2'-FdC also significantly enhanced survival of H1N1-infected mice (50%, p=0.038) similar to the results obtained in the H5N1 infection model using a similar dosing regimen (50%, p<0.05). Given the demonstrated in vitro and in vivo inhibition of avian influenza virus replication, 2'FdC may qualify as a lead compound for the development of agents treating influenza virus infections.
  • |Animals[MESH]
  • |Antiviral Agents/*administration & dosage/pharmacology[MESH]
  • |Cell Line[MESH]
  • |Deoxycytidine/administration & dosage/*analogs & derivatives/pharmacology[MESH]
  • |Dogs[MESH]
  • |Female[MESH]
  • |Histocytochemistry[MESH]
  • |Influenza A Virus, H1N1 Subtype/*drug effects[MESH]
  • |Influenza A Virus, H3N2 Subtype/*drug effects[MESH]
  • |Influenza A Virus, H5N1 Subtype/*drug effects[MESH]
  • |Injections, Intraperitoneal[MESH]
  • |Lung/pathology/virology[MESH]
  • |Mice[MESH]
  • |Mice, Inbred BALB C[MESH]
  • |Microbial Sensitivity Tests[MESH]
  • |Orthomyxoviridae Infections/*drug therapy/*prevention & control/virology[MESH]
  • |Survival Analysis[MESH]


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