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Delivery of Suramin as an Antiviral Agent through Liposomal Systems
Author(s) -
Mastrangelo Eloise,
Mazzitelli Stefania,
Fabbri Jacopo,
Rohayem Jacques,
Ruokolainen Janne,
Nykänen Antti,
Milani Mario,
Pezzullo Margherita,
Nastruzzi Claudio,
Bolognesi Martino
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300563
Subject(s) - suramin , norovirus , liposome , murine norovirus , in silico , in vitro , virology , docking (animal) , biology , enzyme , chemistry , biochemistry , virus , medicine , nursing , gene
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 IC 50 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.