title: Boronic acid-modified lipid nanocapsules: a novel platform for the highly efficient inhibition of hepatitis C viral entry.
abstract: The search for viral entry inhibitors that selectively target viral envelope glycoproteins has attracted increasing interest in recent years. Amongst the handful of molecules reported to show activity as hepatitis C virus (HCV) entry inhibitors are a variety of glycan-binding proteins including the lectins, cyanovirin-N (CV-N) and griffithsin. We recently demonstrated that boronic acid-modified nanoparticles are able to reduce HCV entry through a similar mechanism to that of lectins. A major obstacle to any further development of these nanostructures as viral entry inhibitors is their only moderate maximal inhibition potential. In the present study, we report that lipid nanocapsules (LNCs), surface-functionalized with amphiphilic boronic acid (BA) through their post-insertion into the semi-rigid shell of the LNCs, are indeed far superior as HCV entry inhibitors when compared with previously reported nanostructures. These 2(nd) generation particles (BA-LNCs) are shown to prevent HCV infection in the micromolar range (IC50 = 5.4 μM of BA moieties), whereas the corresponding BA monomers show no significant effects even at the highest analyzed concentration (20 μM). The new BA-LNCs are the most promising boronolectin-based HCV entry inhibitors reported to date and are thus observed to show great promise in the development of a pseudolectin-based therapeutic agent.
authors.affiliation: Institut de Recherche Interdisciplinaire (IRI, USR CNRS 3078), Université Lille 1, Parc de la Haute Borne, 50 Avenue de Halley, BP 70478, 59658 Villeneuve d'Ascq, France. Sabine.Szunerits@iri.univ-lille1.fr.
authors.forename: Manakamana
authors.initials: M
authors.lastname: Khanal
authors.forename: Alexandre
authors.initials: A
authors.lastname: Barras
authors.forename: Thibaut
authors.initials: T
authors.lastname: Vausselin
authors.forename: Lucie
authors.initials: L
authors.lastname: Fénéant
authors.forename: Rabah
authors.initials: R
authors.lastname: Boukherroub
authors.forename: Aloysius
authors.initials: A
authors.lastname: Siriwardena
authors.forename: Jean
authors.initials: J
authors.lastname: Dubuisson
authors.forename: Sabine
authors.initials: S
authors.lastname: Szunerits
mesh_terms: D000906:Antibodies / Q000276:immunology; D001897:Boronic Acids / Q000737:chemistry*; D002232:Carbocyanines / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D008856:Microscopy, Fluorescence; D053769:Nanocapsules / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000906:Antibodies; D001897:Boronic Acids; D002232:Carbocyanines; C087035:E1 protein, Hepatitis C virus; D053769:Nanocapsules; D014280:Triglycerides; D014759:Viral Envelope Proteins; C089187:cyanine dye 3; D011092:Polyethylene Glycols