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Novel oral anti-influenza drug candidate AV5080

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  • Novel oral anti-influenza drug candidate AV5080

    J Antimicrob Chemother. 2014 Apr 11. [Epub ahead of print]
    Novel oral anti-influenza drug candidate AV5080.
    Ivachtchenko AV1, Ivanenkov YA, Mitkin OD, Yamanushkin PM, Bichko VV, Shevkun NA, Karapetian RN, Leneva IA, Borisova OV, Veselov MS.
    Author information
    Abstract
    OBJECTIVES:

    Development of a novel drug candidate with improved potency against influenza virus neuraminidase compared with currently available therapeutics, and high activity against oseltamivir-resistant viruses.
    METHODS:

    A number of synthetic compounds were evaluated for antiviral properties in vitro and in vivo. Three-dimensional molecular docking, assisted by a pharmacophore model, was applied to classify compounds within the series by their inhibitory potency. Compound stability in blood and in animal models was determined. Pharmacokinetic studies in dogs and rats after oral or intravenous administration were performed.
    RESULTS:

    A novel highly potent drug candidate [(3R,4R,5S)-5-[(diaminomethylene)amino]-3-(1-ethylpropoxy)-4-[(fluoroacetyl)amino]cyclohex-1-ene-1-carboxylic acid; AV5080] was synthesized and tested. AV5080 exhibited high activity against influenza virus neuraminidase in vitro, with IC50 values of 0.03 nM and 0.07 nM against the neuraminidase of A/Duck/Minnesota/1525/1981/H5N1 and A/Perth/265/2009/H1N1 (wild-type), respectively. Notably, AV5080 was highly active against oseltamivir-resistant influenza viruses.
    CONCLUSIONS:

    Based on the results presented in this study, AV5080 is a promising novel oral drug candidate for the treatment of influenza, including oseltamivir-resistant types. Further pre-clinical development of AV5080 is warranted.
    KEYWORDS:

    antiviral, neuraminidase inhibitors, pharmacokinetics

    PMID:
    24729605
    [PubMed - as supplied by publisher]

    Based on the results presented in this study, AV5080 is a promising novel oral drug candidate for the treatment of influenza, including oseltamivir-resistant types. Further pre-clinical development of AV5080 is warranted.
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