Delivery of Suramin as an Antiviral Agent through Liposomal Systems

被引:29
作者
Mastrangelo, Eloise [1 ,2 ,3 ]
Mazzitelli, Stefania [4 ]
Fabbri, Jacopo [4 ]
Rohayem, Jacques [5 ,6 ]
Ruokolainen, Janne [7 ]
Nykanen, Antti [7 ]
Milani, Mario [1 ,2 ,3 ]
Pezzullo, Margherita [1 ,2 ,3 ]
Nastruzzi, Claudio [4 ]
Bolognesi, Martino [1 ,2 ,3 ]
机构
[1] Univ Milan, Dept Biosci, I-20133 Milan, Italy
[2] Univ Milan, CIMAINA, I-20133 Milan, Italy
[3] Biophys Inst CNR IBF, I-20133 Milan, Italy
[4] Univ Ferrara, Dept Life Sci & Biotechnol, I-44100 Ferrara, Italy
[5] Tech Univ Dresden, Inst Virol, D-01307 Dresden, Germany
[6] Riboxx GmbH, D-01445 Radebeul, Germany
[7] Aalto Univ, Dept Appl Phys, Espoo 02150, Finland
关键词
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.
引用
收藏
页码:933 / 939
页数:7
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