title: Delivery of suramin as an antiviral agent through liposomal systems.
abstract: 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.
authors.affiliation: Department of Biosciences & CIMAINA, University of Milano, Via Celoria 26, 20133 Milano (Italy); Biophysics Institute (CNR-IBF), Via Celoria 26, 20133 Milano (Italy).
authors.forename: Eloise
authors.initials: E
authors.lastname: Mastrangelo
authors.forename: Stefania
authors.initials: S
authors.lastname: Mazzitelli
authors.forename: Jacopo
authors.initials: J
authors.lastname: Fabbri
authors.forename: Jacques
authors.initials: J
authors.lastname: Rohayem
authors.forename: Janne
authors.initials: J
authors.lastname: Ruokolainen
authors.forename: Antti
authors.initials: A
authors.lastname: Nykänen
authors.forename: Mario
authors.initials: M
authors.lastname: Milani
authors.forename: Margherita
authors.initials: M
authors.lastname: Pezzullo
authors.forename: Claudio
authors.initials: C
authors.lastname: Nastruzzi
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D029322:Norovirus / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D013498:Suramin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D008081:Liposomes; D013498:Suramin
keywords: RNA-dependent RNA polymerase; antiviral agents; drug delivery; liposomes; norovirus