Drug repurposing of minocycline against dengue virus infection

被引:36
|
作者
Leela, Shilpa Lekshmi [1 ,2 ]
Srisawat, Chatchawan [1 ]
Sreekanth, Gopinathan Pillai [3 ]
Noisakran, Sansanee [4 ,5 ]
Yenchitsomanus, Pa-thai [2 ]
Limjindaporn, Thawornchai [3 ]
机构
[1] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Biochem, Bangkok, Thailand
[2] Mahidol Univ, Siriraj Hosp, Fac Med, Div Mol Med,Dept Res & Dev, Bangkok, Thailand
[3] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Anat, Bangkok, Thailand
[4] Natl Sci & Technol Dev Agcy, Natl Canc Ctr Genet Engn & Biotechnol, Med Biotechnol Unit, Bangkok, Thailand
[5] Mahidol Univ, Siriraj Hosp, Fac Med, Div Dengue Hemorrhag Fever Res,Dept Res & Dev, Bangkok, Thailand
关键词
Dengue virus infection; Minocycline; ERK1/2; Antiviral activity; HEPATITIS-C VIRUS; RNASE-L; ANTIVIRAL RESPONSE; ENDOTHELIAL-CELLS; KAPPA-B; REPLICATION; PATHWAY; PROTEIN; ACTIVATION; PATHOGENESIS;
D O I
10.1016/j.bbrc.2016.07.029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dengue virus infection is one of the most common arthropod-borne viral diseases. A complex interplay between host and viral factors contributes to the severity of infection. The antiviral effects of three antibiotics, lomefloxacin, netilmicin, and minocycline, were examined in this study, and minocycline was found to be a promising drug. This antiviral effect was confirmed in all four serotypes of the virus. The effects of minocycline at various stages of the viral life cycle, such as during viral RNA synthesis, intracellular envelope protein expression, and the production of infectious virions, were examined and found to be significantly reduced by minocycline treatment. Minocycline also modulated host factors, including the phosphorylation of extracellular signal-regulated kinasel/2 (ERK1/2). The transcription of antiviral genes, including 2'-5'-oligoadenylate synthetase 1 (OAST), 2'-5'-oligoadenylate synthetase 3 (OAS3), and interferon alpha (IFNA), was upregulated by minocycline treatment. Therefore, the antiviral activity of minocycline may have a potential clinical use against Dengue virus infection. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:410 / 416
页数:7
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