Injectable peramivir mitigates disease and promotes survival in ferrets and mice infected with the highly virulent influenza virus, A/Vietnam/1203/04 (H5N1)

被引:56
作者
Yun, Nadezhda E. [1 ]
Linde, Nathaniel S. [1 ]
Zacks, Michele A. [1 ]
Barr, Ian G. [2 ]
Hurt, Aeron C. [2 ]
Smith, Jeanon N. [1 ]
Dziuba, Natallia [1 ]
Holbrook, Michael R. [1 ]
Zhang, Lifang [3 ]
Kilpatrick, John M. [4 ]
Arnold, C. Shane [4 ]
Paessler, Slobodan [1 ]
机构
[1] Univ Texas Galveston, Med Branch, Dept Pathol, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA
[2] WHO Collaborating, Ctr Influenza, Melbourne, Vic, Australia
[3] Univ Texas Galveston, Med Branch, Dept Prevent Med & Community Hlth, Biostat Off, Galveston, TX 77555 USA
[4] BioCryst Pharmaceut Inc, Birmingham, AL USA
关键词
influenza a virus; avian influenza; pathogenicity; antiviral agents; animal model; virulence; peramivir;
D O I
10.1016/j.virol.2007.12.029
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The post-exposure therapeutic efficacy of injectable peramivir against highly pathogenic avian influenza type A H5N1 was evaluated in mice and in ferrets. Seventy to eighty percent of the H5N1-infected peramivir-treated mice, and 70% in the oseltamivir treated mice survived the 15-day study period, as compared to 36% in control (vehicle) group. Ferrets were infected intranasally with H5N1 followed by treatment with multiple doses of peramivir. In two of three trials, a statistically significant increase in survival over a 16-18 day period resulted from peramivir treatment, with improved survival of 40-64% in comparison to mock-treated of untreated animals. Injected peramivir mitigates virus-induced disease, reduces infectious virus titers in the lungs and brains and promotes survival in ferrets infected intranasally with this highly neurovirulent isolate. A single intramuscular peramivir injection protected mice against severe disease outcomes following infection with highly pathogenic avian influenza and multi-dose treatment was efficacious in ferrets. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:198 / 209
页数:12
相关论文
共 68 条
[1]   Characterization of 2 influenza A(H3N2) clinical isolates with reduced susceptibility to neuraminidase inhibitors due to mutations in the hemagglutinin gene [J].
Abed, Y ;
Bourgault, AM ;
Fenton, RJ ;
Morley, PJ ;
Gower, D ;
Owens, IJ ;
Tisdale, M ;
Boivin, G .
JOURNAL OF INFECTIOUS DISEASES, 2002, 186 (08) :1074-1080
[2]  
[Anonymous], 2006, Wkly Epidemiol Rec, V81, P249
[3]   BCX-1812 (RWJ-270201): Discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design [J].
Babu, YS ;
Chand, P ;
Bantia, S ;
Kotian, P ;
Dehghani, A ;
El-Kattan, Y ;
Lin, TH ;
Hutchison, TL ;
Elliott, AJ ;
Parker, CD ;
Ananth, SL ;
Horn, LL ;
Laver, GW ;
Montgomery, JA .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (19) :3482-3486
[4]   Anti-influenza virus activity of peramivir in mice with single intramuscular injection [J].
Bantia, S ;
Arnold, CS ;
Parker, CD ;
Upshaw, R ;
Chand, P .
ANTIVIRAL RESEARCH, 2006, 69 (01) :39-45
[5]   Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir [J].
Bantia, S ;
Parker, CD ;
Ananth, SL ;
Horn, LL ;
Andries, K ;
Chand, P ;
Kotian, PL ;
Dehghani, A ;
El-Kattan, Y ;
Lin, T ;
Hutchison, TL ;
Montgomery, JA ;
Kellog, DL ;
Babu, YS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (04) :1162-1167
[6]  
Barnard D L, 2000, Curr Opin Investig Drugs, V1, P421
[7]   Characterization of drug-resistant recombinant influenza A/H1N1 viruses selected in vitro with peramivir and zanamivir [J].
Baz, Mariana ;
Abed, Yacine ;
Boivin, Guy .
ANTIVIRAL RESEARCH, 2007, 74 (02) :159-162
[8]   Current concepts - Avian influenza A (H5N1) infection in humans [J].
Beigel, H ;
Farrar, H ;
Han, AM ;
Hayden, FG ;
Hyer, R ;
de Jong, MD ;
Lochindarat, S ;
Tien, NTK ;
Hien, NT ;
Hien, TT ;
Nicoll, A ;
Touch, S ;
Yuen, KY .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (13) :1374-1385
[9]  
Borroso L, 2005, ANTIVIR THER, V10, P901
[10]  
Boyd M, 2006, MED J AUSTRALIA, V185, pS44