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 50mg/kg/day for 5days 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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