title: The inhibitory effect of dehydroepiandrosterone and its derivatives against influenza A virus in vitro and in vivo.
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.
authors: Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People's Republic of China.
authors: Qingyu
authors: Q
authors: Yang
authors: Department of Urology, Renmin Hospital, Wuhan University, Wuhan, 430060, People's Republic of China.
authors: Qing
authors: Q
authors: Mao
authors: Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People's Republic of China.
authors: Manli
authors: M
authors: Liu
authors: Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People's Republic of China.
authors: Kaimei
authors: K
authors: Wang
authors: Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People's Republic of China.
authors: Zhaoyuan
authors: Z
authors: Wu
authors: Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People's Republic of China.
authors: Wei
authors: W
authors: Fang
authors: Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People's Republic of China.
authors: Ziwen
authors: Z
authors: Yang
authors: Department of Urology, Renmin Hospital, Wuhan University, Wuhan, 430060, People's Republic of China.|Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi, 435000, People's Republic of China.
authors: Pengchen
authors: P
authors: Luo
authors: Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People's Republic of China. keshaoyong@163.com.
authors: Shaoyong
authors: http://orcid.org/0000-0001-5165-4694
authors: S
authors: Ke
authors: Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, People's Republic of China. shiliqiao_75@163.com.|Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi, 435000, People's Republic of China. shiliqiao_75@163.com.
authors: Liqiao
authors: L
authors: Shi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D003687:Dehydroepiandrosterone