Glycofullerenes Inhibit Viral Infection

Abstract

Water-soluble glycofullerenes based on a hexakis-adduct of [60]fullerene with an octahedral addition pattern are very attractive compounds providing a spherical presentation of carbohydrates. These tools have been recently described and they have been used to interact with lectins in a multivalent manner. Here, we present the use of these glycofullerenes, including new members with 36 mannoses, as compounds able to inhibit a DC-SIGN-dependent cell infection by pseudotyped viral particles. The results obtained in these experiments demonstrate for the first time that these glycoconjugates are adequate to inhibit efficiently an infection process, and therefore, they can be considered as very promising and interesting tools to interfere in biological events where lectins such as DC-SIGN are involved.

Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

“…This longer spacer affects the flexibility and the size of the compound and can favor the accessibility and availability of the carbohydrate ligands to interact with the receptor, which could have an important influence on the biological activity. 20 It is important to note, however, that the aforementioned synthetic approaches allow synthesizing fullerene derivatives from malonates endowed with alkyl chains of variable length through a first Bingel cyclopropanation and a subsequent CuAAC reaction. This synthetic strategy affords hexakis-adducts with long chains connecting the fullerenes and carbohydrates since their direct preparation from suitably functionalized malonates bearing long chains typically occur with remarkably low yields.…”

“…19 Furthermore, studies carried out on hexakis-adducts of [60]fullerene endowed with 12, 24 and 36 mannoses have shown a multivalent effect in the interaction with Concanavalin A, 15 and acting as efficient inhibitors of cell infection by Ebola pseudotyped viral particles. 20 These preliminary studies reveal that fullerenes are adequate platforms for the multivalent presentation of carbohydrates, thus paving the way to the covalent linkage of a wide variety of different bio-active molecules in a multivalent manner and a singular and less-explored globular topology.…”

Glycoconjugates and Glycomimetics as Microbial Anti-Adhesives

“…The dendrimer was also found to inhibit the interaction between DC-SIGN and gp120 immobilized on an SPR sensor with an IC 50 in the micromolar range (IC 50 50 µM) [57]. To the same end, also water-soluble manno-fullerenes [58], and virus-like manno-dendronanoparticles capable of mimicking pathogens both in size and in their highly glycosylated surfaces [59], were explored (Figure 3a). The latter were built using as platform Qβ, a recombinant capsid protein derived from the bacteriophage Qβ that spontaneously self-assemble to give icosahedral virus-like particles of 25 nm ca.…”

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

“…The dendrimers with certain clustered mannose structures were capable of blocking viral binding to DC-SIGN (at picomolar concentrations) in a model where Tlymphocytes and human dendritic cells were infected by the Ebola virus [58]. Moreover, soluble glycofullerenes have shown interesting antiviral activity in an Ebola pseudotyped infection model, thus opening new perspectives for their applications [61]. Serum-derived circulating mannose-binding lectins (MBL) and recombinant human MBL (rhMBL) demonstrated the potential utility against Ebola [62].…”