title: Multivalent Glycosylated Nanostructures To Inhibit Ebola Virus Infection.
abstract: The infection of humans by lethal pathogens such as Ebola and other related viruses has not been properly addressed so far. In this context, a relevant question arises: What can chemistry do in the search for new strategies and approaches to solve this emergent problem? Although initially a variety of known chemical compounds-for other purposes-proved disappointing in tests against Ebola virus (EBOV) infection, more recently, specific molecules have been prepared. In this Perspective, we present new approaches directed at the design of efficient entry inhibitors to minimize the development of resistance by viral mutations. In particular, we focus on dendrimers as well as fullerene C60-with a unique symmetrical and 3D globular structure-as biocompatible carbon platforms for the multivalent presentation of carbohydrates. The antiviral activity of these compounds in an Ebola pseudotyped infection model was in the low micromolar range for fullerenes with 12 and 36 mannoses. However, new tridecafullerenes-in which the central alkyne scaffold of [60]fullerene is connected to 12 sugar-containing [60]fullerene units (total 120 mannoses)-exhibit an outstanding antiviral activity with IC50in the sub-nanomolar range! The multivalent presentation of specific carbohydrates by using 3D fullerenes as controlled biocompatible carbon scaffolds represents a real advance, being currently the most efficient molecules in vitro against EBOV infection. However, additional studies are needed to determine the optimized fullerene-based leads for practical applications.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad Complutense , 28040 Madrid, Spain.
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Illescas
authors.affiliation: Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla , Av. Américo Vespucio 49, 41092 Seville, Spain.
authors.forename: Javier
authors.identifier: 0000-0003-3173-3437
authors.initials: J
authors.lastname: Rojo
authors.affiliation: Laboratorio de Microbiología Molecular, Instituto de Investigación Hospital 12 de Octubre (imas12) , 28041 Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Delgado
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad Complutense , 28040 Madrid, Spain.
authors.forename: Nazario
authors.identifier: 0000-0002-5355-1477
authors.initials: N
authors.lastname: Martín
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D029043:Ebolavirus / Q000187:drug effects* / Q000235:genetics; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009154:Mutation; D049329:Nanostructures / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D050091:Dendrimers; D037741:Fullerenes; C069837:fullerene C60