antiviral agents;
drug delivery;
liposomes;
norovirus;
RNA-dependent RNA polymerase;
NOROVIRUS;
D O I:
10.1002/cmdc.201300563
中图分类号:
R914 [药物化学];
学科分类号:
100705 [微生物与生化药学];
摘要:
Norovirus RNA-dependent RNA polymerase (RdRp) is a promising target enzyme for the development of new antiviral drugs. Starting from the crystal structure of norovirus RdRp, we had previously performed an in silico docking search using a library of low-molecular-weight compounds that enabled us to select molecules with predicted enzyme inhibitory activity. Among these, the polysulfonated naphthylurea suramin proved to inhibit in vitro both murine and human norovirus polymerases, with IC50 values in the low micromolar range. The negatively charged inhibitor, however, displayed poor cell permeability in cell-based experiments. Therefore, we produced different suramin-loaded liposome formulations and evaluated their activities in cell-based assays using murine norovirus cultivated in RAW 264.7 macrophages, as a model for norovirus genus. The results obtained show that suramin, when delivered through liposomes, can effectively inhibit murine norovirus replication.
机构:
Chang Gung Mem Hosp, Div Pediat Gastroenterol, Tao Yuan 333, Taiwan
Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Tao Yuan, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Chen, Shih-Yen
;
论文数: 引用数:
h-index:
机构:
Tsai, Chi-Neu
;
Lai, Ming-Wei
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Div Pediat Gastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Lai, Ming-Wei
;
Chen, Chih-Yen
论文数: 0引用数: 0
h-index: 0
机构:
Da Yeh Univ, Dept Mol Biotechnol, Changhua, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Chen, Chih-Yen
;
Lin, Kuang-Lin
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Div Pediat Neurol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Lin, Kuang-Lin
;
Lin, Tzou-Yien
论文数: 0引用数: 0
h-index: 0
机构:Chang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Lin, Tzou-Yien
;
Chiu, Cheng-Hsun
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
机构:
Chang Gung Mem Hosp, Div Pediat Gastroenterol, Tao Yuan 333, Taiwan
Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Tao Yuan, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Chen, Shih-Yen
;
论文数: 引用数:
h-index:
机构:
Tsai, Chi-Neu
;
Lai, Ming-Wei
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Div Pediat Gastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Lai, Ming-Wei
;
Chen, Chih-Yen
论文数: 0引用数: 0
h-index: 0
机构:
Da Yeh Univ, Dept Mol Biotechnol, Changhua, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Chen, Chih-Yen
;
Lin, Kuang-Lin
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Div Pediat Neurol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Lin, Kuang-Lin
;
Lin, Tzou-Yien
论文数: 0引用数: 0
h-index: 0
机构:Chang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan
Lin, Tzou-Yien
;
Chiu, Cheng-Hsun
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Dept Pediat, Div Pediat Infect Dis, Tao Yuan 333, Taiwan