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The inhibitory effect of dehydroepiandrosterone and its derivatives against influenza A virus in vitro and in vivo

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  • The inhibitory effect of dehydroepiandrosterone and its derivatives against influenza A virus in vitro and in vivo

    Arch Virol. 2016 Aug 12. [Epub ahead of print]
    The inhibitory effect of dehydroepiandrosterone and its derivatives against influenza A virus in vitro and in vivo.

    Yang Q1, Mao Q2, Liu M1, Wang K1, Wu Z1, Fang W1, Yang Z1, Luo P2,3, Ke S4, Shi L5,6.
    Author information

    Abstract

    The antiviral activity of dehydroepiandrosterone (DHEA) and 21 synthetic derivatives against influenza A virus (IAV) replication was investigated in vitro in cell culture. Our results revealed that three DHEA analogues were potent inhibitors of IAV multiplication in MDCK cells and mainly blocked the post-attachment stage of viral infection. Among these derivatives, one containing a 2-OH-Ph moiety (3i) exhibited the best inhibitory effects against H1N1 and H3N2 IAV in a dose-dependent manner. Moreover, treatment with compound 3i decreased progeny virus yields, viral RNA synthesis and protein expression. Orally administered compound 3i at 25 or 50 mg/kg/day for 5 days protected mice from lethal A/FM/1/47 (H1N1) challenge by reducing the viral titers in the lungs and promoting survival of infected mice. Our results suggest that DHEA-dihydrazone derivatives may provide promising lead scaffolds for further design and synthesis of potential antiviral agents.


    PMID: 27518401 DOI: 10.1007/s00705-016-2993-6
    [PubMed - as supplied by publisher]
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