4.5 Article

Delivery of Suramin as an Antiviral Agent through Liposomal Systems

期刊

CHEMMEDCHEM
卷 9, 期 5, 页码 933-939

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201300563

关键词

antiviral agents; drug delivery; liposomes; norovirus; RNA-dependent RNA polymerase

资金

  1. European Union [260644]

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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.

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