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Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses.

Abstract

The orally administered neuraminidase (NA) inhibitor RWJ-270201 was tested in parallel with zanamivir and oseltamivir against a panel of avian influenza viruses for inhibition of NA activity and replication in tissue culture. The agents were then tested for protection of mice against lethal H5N1 and H9N2 virus infection. In vitro, RWJ-270201 was highly effective against all nine NA subtypes. NA inhibition by RWJ-270201 (50% inhibitory concentration, 0.9 to 4.3 nM) was superior to that by zanamivir and oseltamivir carboxylate. RWJ-270201 inhibited the replication of avian influenza viruses of both Eurasian and American lineages in MDCK cells (50% effective concentration, 0.5 to 11.8 microM). Mice given 10 mg of RWJ-270201 per kg of body weight per day were completely protected against lethal challenge with influenza A/Hong Kong/156/97 (H5N1) and A/quail/Hong Kong/G1/97 (H9N2) viruses. Both RWJ-270201 and oseltamivir significantly reduced virus titers in mouse lungs at daily dosages of 1.0 and 10 mg/kg and prevented the spread of virus to the brain. When treatment began 48 h after exposure to H5N1 virus, 10 mg of RWJ-270201/kg/day protected 50% of mice from death. These results suggest that RWJ-270201 is at least as effective as either zanamivir or oseltamivir against avian influenza viruses and may be of potential clinical use for treatment of emerging influenza viruses that may be transmitted from birds to humans.

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  • Authors+Show Affiliations

    ,

    Department of Virology and Molecular Biology, St. Jude's Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.

    , , ,

    Source

    Antimicrobial agents and chemotherapy 45:10 2001 Oct pg 2723-32

    MeSH

    Acetamides
    Animals
    Antiviral Agents
    Body Weight
    Brain
    Cyclopentanes
    Disease Models, Animal
    Dogs
    Female
    Guanidines
    Influenza A Virus, H5N1 Subtype
    Influenza A Virus, H9N2 Subtype
    Influenza A virus
    Lung
    Mice
    Mice, Inbred BALB C
    Neuraminidase
    Orthomyxoviridae Infections
    Oseltamivir
    Pyrans
    Sialic Acids
    Treatment Outcome
    Virus Replication
    Zanamivir

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    11557461

    Citation

    Govorkova, E A., et al. "Comparison of Efficacies of RWJ-270201, Zanamivir, and Oseltamivir Against H5N1, H9N2, and Other Avian Influenza Viruses." Antimicrobial Agents and Chemotherapy, vol. 45, no. 10, 2001, pp. 2723-32.
    Govorkova EA, Leneva IA, Goloubeva OG, et al. Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob Agents Chemother. 2001;45(10):2723-32.
    Govorkova, E. A., Leneva, I. A., Goloubeva, O. G., Bush, K., & Webster, R. G. (2001). Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrobial Agents and Chemotherapy, 45(10), pp. 2723-32.
    Govorkova EA, et al. Comparison of Efficacies of RWJ-270201, Zanamivir, and Oseltamivir Against H5N1, H9N2, and Other Avian Influenza Viruses. Antimicrob Agents Chemother. 2001;45(10):2723-32. PubMed PMID: 11557461.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. AU - Govorkova,E A, AU - Leneva,I A, AU - Goloubeva,O G, AU - Bush,K, AU - Webster,R G, PY - 2001/9/15/pubmed PY - 2002/1/5/medline PY - 2001/9/15/entrez SP - 2723 EP - 32 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 45 IS - 10 N2 - The orally administered neuraminidase (NA) inhibitor RWJ-270201 was tested in parallel with zanamivir and oseltamivir against a panel of avian influenza viruses for inhibition of NA activity and replication in tissue culture. The agents were then tested for protection of mice against lethal H5N1 and H9N2 virus infection. In vitro, RWJ-270201 was highly effective against all nine NA subtypes. NA inhibition by RWJ-270201 (50% inhibitory concentration, 0.9 to 4.3 nM) was superior to that by zanamivir and oseltamivir carboxylate. RWJ-270201 inhibited the replication of avian influenza viruses of both Eurasian and American lineages in MDCK cells (50% effective concentration, 0.5 to 11.8 microM). Mice given 10 mg of RWJ-270201 per kg of body weight per day were completely protected against lethal challenge with influenza A/Hong Kong/156/97 (H5N1) and A/quail/Hong Kong/G1/97 (H9N2) viruses. Both RWJ-270201 and oseltamivir significantly reduced virus titers in mouse lungs at daily dosages of 1.0 and 10 mg/kg and prevented the spread of virus to the brain. When treatment began 48 h after exposure to H5N1 virus, 10 mg of RWJ-270201/kg/day protected 50% of mice from death. These results suggest that RWJ-270201 is at least as effective as either zanamivir or oseltamivir against avian influenza viruses and may be of potential clinical use for treatment of emerging influenza viruses that may be transmitted from birds to humans. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/11557461/Comparison_of_efficacies_of_RWJ_270201_zanamivir_and_oseltamivir_against_H5N1_H9N2_and_other_avian_influenza_viruses_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=11557461 DB - PRIME DP - Unbound Medicine ER -