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

被引：14

作者：

Yang, Qingyu ^{[1
]}

Mao, Qing ^{[2
]}

Liu, Manli ^{[1
]}

Wang, Kaimei ^{[1
]}

Wu, Zhaoyuan ^{[1
]}

Fang, Wei ^{[1
]}

Yang, Ziwen ^{[1
]}

Luo, Pengchen ^{[2
,3
]}

Ke, Shaoyong ^{[1
]}

Shi, Liqiao ^{[1
,3
]}

机构：

[1] Hubei Acad Agr Sci, Hubei Biopesticide Engn Res Ctr, Wuhan 430064, Peoples R China

[2] Wuhan Univ, Renmin Hosp, Dept Urol, Wuhan 430060, Peoples R China

[3] Hubei Key Lab Kidney Dis Pathogenesis & Intervent, Huangshi 435000, Peoples R China

来源：

ARCHIVES OF VIROLOGY | 2016年 / 161卷 / 11期

关键词：

ANTIVIRAL ACTIVITY; INFECTION; TYPE-1; AGENTS;

D O I：

10.1007/s00705-016-2993-6

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：3061 / 3072

页数：12

共 30 条

[1] Screening methods for influenza antiviral drug discovery [J].

Atkins, Colm ;

Evans, Carrie W. ;

White, E. Lucile ;

Noah, James W. .

EXPERT OPINION ON DRUG DISCOVERY, 2012, 7 (05) :429-438

[2] Immunomodulatory effects of zinc and DHEA on the Th-1 immune response in rats infected with Trypanosoma cruzi [J].

Brazao, Vania ;

Santello, Fabricia Helena ;

Caetano, Leony Cristina ;

Filipin, Marina Del Vecchio ;

Alonso Toldo, Miriam Paula ;

do Prado, Jose Clovis, Jr. .

IMMUNOBIOLOGY, 2010, 215 (05) :427-434

[3] Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus infection [J].

Chang, CC ;

Ou, YC ;

Raung, SL ;

Chen, CJ .

JOURNAL OF GENERAL VIROLOGY, 2005, 86 :2513-2523

[4]

Daigle J, 1998, J IMMUNOL, V160, P3060

[5] Antiviral agents active against influenza A viruses [J].

De Clercq, Erik .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (12) :1015-1025

[6] Inhibition of human immunodeficiency virus type-1 (HIV-1) replication by Immunor (IM28), a new analog of dehydroepiandrosterone [J].

Diallo, K ;

Loemba, H ;

Oliveira, M ;

Mavoungou, DD ;

Wainberg, MA .

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2000, 19 (10-12) :2019-2024

[7]

Flu. Gov, 2015, PAND FLU HIST

[8] DEHYDROEPIANDROSTERONE AND 16-ALPHA-BROMO-EPIANDROSTERONE - INHIBITORS OF EPSTEIN-BARR VIRUS-INDUCED TRANSFORMATION OF HUMAN-LYMPHOCYTES [J].

HENDERSON, E ;

SCHWARTZ, A ;

PASHKO, L ;

ABOUGHARBIA, M ;

SWERN, D .

CARCINOGENESIS, 1981, 2 (07) :683-686

[9]

Hurt Aeron C, 2006, Expert Rev Anti Infect Ther, V4, P795, DOI 10.1586/14787210.4.5.795

[10] Synthesis of Novel Steroid Derivatives Derived from Dehydroepiandrosterone as Potential Anticancer Agents [J].

Ke, Shaoyong ;

Wei, Yanhong ;

Shi, Liqiao ;

Yang, Qingyu ;

Yang, Ziwen .

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2013, 13 (08) :1291-1298

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