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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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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.

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Acknowledgements

This work was financially supported by Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention (SB201410) and the Supportive Projects of Hubei Academy of Agricultural Sciences (2014fcxjh17). The authors also gratefully acknowledge the partial support from Hubei Agricultural Science Innovation Centre (2012-620-008-002).

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Authors and Affiliations

  1. Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People’s Republic of China

    Qingyu Yang, Manli Liu, Kaimei Wang, Zhaoyuan Wu, Wei Fang, Ziwen Yang, Shaoyong Ke & Liqiao Shi

  2. Department of Urology, Renmin Hospital, Wuhan University, Wuhan, 430060, People’s Republic of China

    Qing Mao & Pengchen Luo

  3. Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi, 435000, People’s Republic of China

    Pengchen Luo & Liqiao Shi

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  1. Qingyu Yang
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  2. Qing Mao
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Correspondence to Shaoyong Ke or Liqiao Shi.

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Yang, Q., Mao, Q., Liu, M. et al. The inhibitory effect of dehydroepiandrosterone and its derivatives against influenza A virus in vitro and in vivo . Arch Virol 161, 3061–3072 (2016). https://doi.org/10.1007/s00705-016-2993-6

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  • DOI: https://doi.org/10.1007/s00705-016-2993-6

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