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Multivalent Glycosylated Nanostructures To Inhibit Ebola Virus Infection.
- Source :
-
Journal of the American Chemical Society [J Am Chem Soc] 2017 May 03; Vol. 139 (17), pp. 6018-6025. Date of Electronic Publication: 2017 Apr 20. - Publication Year :
- 2017
-
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 C <subscript>60</subscript> -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 IC <subscript>50</subscript> in 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.
- Subjects :
- Antiviral Agents chemistry
Dendrimers chemistry
Ebolavirus genetics
Fullerenes chemistry
Glycosylation
Humans
Microbial Sensitivity Tests
Molecular Structure
Mutation
Antiviral Agents pharmacology
Dendrimers pharmacology
Ebolavirus drug effects
Fullerenes pharmacology
Hemorrhagic Fever, Ebola drug therapy
Nanostructures chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5126
- Volume :
- 139
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Journal of the American Chemical Society
- Publication Type :
- Academic Journal
- Accession number :
- 28394600
- Full Text :
- https://doi.org/10.1021/jacs.7b01683