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

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...

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Bibliographic Details
Published in:Archives of virology 2016-11, Vol.161 (11), p.3061-3072
Main Authors: Yang, Qingyu, Mao, Qing, Liu, Manli, Wang, Kaimei, Wu, Zhaoyuan, Fang, Wei, Yang, Ziwen, Luo, Pengchen, Ke, Shaoyong, Shi, Liqiao
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Biomedical and Life Sciences
Biomedicine
Cytotoxicity
Dehydroepiandrosterone - analogs & derivatives
Dehydroepiandrosterone - pharmacology
Dehydroepiandrosterone - therapeutic use
Disease Models, Animal
Dogs
Drug resistance
Epidemics
Humans
Infections
Infectious Diseases
Influenza A virus
Influenza A virus - drug effects
Influenza A virus - physiology
Madin Darby Canine Kidney Cells
Medical Microbiology
Mice, Inbred BALB C
Original Article
Orthomyxoviridae
Orthomyxoviridae Infections - drug therapy
Pandemics
Steroids
Survival Analysis
Treatment Outcome
Viral infections
Virology
Virus Replication - drug effects
Viruses
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Summary: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.
ISSN:0304-8608
1432-8798
DOI:10.1007/s00705-016-2993-6