LitCovid-sentences  

PMC:7376974 / 35188-43746 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T219 0-15 Sentence denotes Glycofullerenes
T220 16-195 Sentence denotes The emerging of mortal viruses, like Ebola or Zika, and the lack of suitable treatments led the academic and the industrial communities to look for alternative therapeutic routes.
T221 196-359 Sentence denotes Most of these pathogens are RNA enveloped viruses, and they share common infection mechanisms that can be targeted for the preparation of wide spectrum antivirals.
T222 360-614 Sentence denotes The external surface of the envelope of these viruses is covered by glycans that tightly interact with lectin receptors on host cells.64 This strong interaction allows the attachment of the virions to the cells, followed by internalization and infection.
T223 615-710 Sentence denotes Blocking lectin receptors is a general strategy used to stop viral infection at an early stage.
T224 711-961 Sentence denotes Fullerenes have been widely investigated as antiviral molecules, drug carriers, or tissue scaffolds.65 Fullerene applications have been recently extended to the design of mannosylated derivatives to block the entry of viral particles into host cells.
T225 962-1082 Sentence denotes Mannose, due to the high affinity with lectin receptors, competes with the virus in the interaction with the host cells.
T226 1083-1257 Sentence denotes For example, one of the targets is the inhibition of viral particles through the interaction of mannose with the dendritic cell-specific ICAM-grabbing non-integrin (DC-sign).
T227 1258-1518 Sentence denotes DC-sign receptors mediate the interactions between DCs and T cells.66,67 To exploit these characteristics, mannose was combined with fullerene in the design of the so-called glycofullerenes to study their capacity to inhibit Ebola, Dengue, and other pathogens.
T228 1519-2053 Sentence denotes For this purpose, different glycofullerenes were synthesized by changing the number of mannose units (from 12 to 36) and the spacers between the fullerene moieties and by varying steric hindrance in order to obtain a library of molecules.66 The synthetic route is composed of three steps based on “click chemistry”: (1) assembly of glycodendrons by Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC), (2) synthesis of alkyne-substituted Bingel-Hirsch hexakis-adducts, and (3) the coupling between the last two products again by CuAAC.
T229 2054-2185 Sentence denotes To increase the number of mannose moieties up to 36, the glycodendron core was changed from malonate to trialkynyl pentaerythritol.
T230 2186-2265 Sentence denotes In order to compare the different derivatives, in vitro studies were performed.
T231 2266-2450 Sentence denotes Jurkat cells (lymphocyte T CD4 immortalized cells) expressing DC-sign were used to prove the inhibition capacity of the glycofullerenes on viral infection of Ebola (Figure 6, route A).
T232 2451-2758 Sentence denotes The study revealed an IC50 in the μM range for the 12 mannose fullerene, a lower efficiency with the 36 mannose fullerene with a short spacer (PEG, with 2 ethylene oxide units), while a nanomolar IC50 was achieved with 36 mannose fullerenes with a longer spacer (PEG, with 3 ethylene oxide units) (Table 3).
T233 2759-2927 Sentence denotes This first proof-of-concept study was then expanded, aiming to obtain a better antiviral activity by increasing the valence and inserting longer and flexible spacers.68
T234 2928-3017 Sentence denotes Figure 6 Chemical design and general scheme to block the viral entry by glycofullerenes.
T235 3018-3320 Sentence denotes Three different shapes of glycofullerenes can act as inhibitor of viral infection: (A) shape composed of monodisperse fullerene bearing mannose, (B) assembly as “sugar balls” of tridecafullerenes exhibiting mannose on the edges, and (C) supramolecular micellar aggregates of fullerenes bearing mannose.
T236 3321-3400 Sentence denotes Table 3 Antiviral Activity of Different Fullerenes Functionalized with Mannose
T237 3401-3536 Sentence denotes material functional groups core function number of mannose moieties virus number of atoms between fullerene and mannose IC50 ref
T238 3537-3603 Sentence denotes glycofullerene monosaccharide malonate 12 Ebola 8 2 μM (66)
T239 3604-3684 Sentence denotes glycofullerene monosaccharide trialkynyl pentaerythritol 36 Ebola 22 68 μM
T240 3685-3766 Sentence denotes glycofullerene monosaccharide trialkynyl pentaerythritol 36 Ebola 28 0.3 μM
T241 3767-3844 Sentence denotes trideca-fullerenesa monosaccharide malonate 120 Ebola 8 20.375 nM (69)
T242 3845-3915 Sentence denotes trideca-fullerenesb monosaccharide malonate 120 Ebola 8 0.667 nM
T243 3916-4001 Sentence denotes glycofullerene disaccharide trialkynyl pentaerythritol 36 Zika 29 8.35 nM (70)
T244 4002-4017 Sentence denotes Dengue 7.71 nM
T245 4018-4102 Sentence denotes trideca-fullerenes disaccharide trialkynyl pentaerythritol 120 Zika 29 0.52 nM
T246 4103-4119 Sentence denotes Dengue 0.098 nM
T247 4120-4205 Sentence denotes trideca-fullerenes disaccharide trialkynyl pentaerythritol 360 Zika 48 0.067 nM
T248 4206-4222 Sentence denotes Dengue 0.035 nM
T249 4223-4319 Sentence denotes micellar glycofullerenes monosaccharide trialkynyl pentaerythritol 6 Ebola 23 424 nM (72)
T250 4320-4411 Sentence denotes micellar glycofullerenes monosaccharide trialkynyl pentaerythritol 12 Ebola 25 196 nM
T251 4412-4472 Sentence denotes a Small spacer between core C60 and surrounding fullerenes.
T252 4473-4533 Sentence denotes b Large spacer between core C60 and surrounding fullerenes.
T253 4534-4626 Sentence denotes Based on these studies, another class of multivalent fullerene dendrimers was then designed.
T254 4627-4770 Sentence denotes A fast and controlled synthetic route was developed to achieve giant globular multivalent fullerenes, containing hundreds of functional groups.
T255 4771-4948 Sentence denotes The first study was performed with tridecafullerenes containing 120 mannoses.69 The molecular structure is composed of 12 hexakis C60 surrounding a C60 core (Figure 6, route B).
T256 4949-5253 Sentence denotes Compared to the previous study, an IC50 3 orders of magnitude lower was measured on the inhibition of Ebola virus (Table 3).66,68 In order to present more carbohydrates at the periphery of the dendrimer, a trialkynyl pentaerythritol derivative allowed to afford a tridecafullerene with 360 carbohydrates.
T257 5254-5676 Sentence denotes In this case, the molecule was synthesized with a C60 tridecafullerene bearing α(1,2)mannobioside.70 The use of this disaccharide was already investigated, showing an increase of affinity with DC-sign receptors by a factor of 3–4.71 The synthetic strategy exploited also the use of strain-promoted copper-free cycloaddition of azides to alkynes (SPAAC) for the coupling of the core fullerene to the surrounding fullerenes.
T258 5677-5759 Sentence denotes SPAAC allows an easier purification avoiding the removal of cytotoxic copper ions.
T259 5760-5871 Sentence denotes The inhibition performance of this molecule was studied in vitro with viral pseudoparticles of Dengue and Zika.
T260 5872-5982 Sentence denotes The comparison was made between 360 and 120 disaccharides tridecafullerenes and 36 disaccharide monofullerene.
T261 5983-6116 Sentence denotes The results highlighted a picomolar IC50 inhibition on both Zika and Dengue models for the 360 disaccharide glycofullerene (Table 3).
T262 6117-6231 Sentence denotes The ability to inhibit other types of viruses allows the use of glycofullerenes as broad spectrum antiviral drugs.
T263 6232-6328 Sentence denotes Moreover, the negligible toxicity to other cells proved the biocompatibility of these molecules.
T264 6329-6561 Sentence denotes Following an alternative strategy, a supramolecular assembly of monodisperse glycofullerenes, leading to the formation of micelles, was achieved and tested.72 These micelles present a uniform and spherical shape (Figure 6, route C).
T265 6562-6766 Sentence denotes The aggregation synthetic route is faster compared to a controlled synthesis of giant glycofullerenes, but it might suffer from low reproducibility and batch-to-batch differences between each formulation.
T266 6767-7030 Sentence denotes This self-assembled C60 functionalized with 6 or 12 mannoses exposes a large amount of carbohydrate at the surface, leading to an inhibition of Ebola virus in the nanomolar range (IC50 of 424 nM for six mannoses and 196 nM for 12 mannoses, respectively, Table 3).
T267 7031-7121 Sentence denotes Further in vitro studies evidenced again a good biocompatibility of these glycofullerenes.
T268 7122-7259 Sentence denotes While there are no in vivo studies yet, these promising results enlarge the panel of molecules in the fight against new emerging viruses.
T269 7260-7390 Sentence denotes Functionalized fullerenes have been used for their ability to compete with viral particles through lectin receptors in host cells.
T270 7391-7631 Sentence denotes There has been a tremendous advancement in the functionalization of fullerenes leading to the preparation of derivatives with a high amount of mannose, capable to enhance the multivalency effect and thus to increase the therapeutic outcome.
T271 7632-7699 Sentence denotes First, glycofullerenes do not have an intrinsic virucidal activity.
T272 7700-7790 Sentence denotes They can reduce the infectivity, but they are not able to completely inactivate the virus.
T273 7791-7915 Sentence denotes Second, the mechanism of action of glycofullerenes relies on their interaction with host cells and not with viral particles.
T274 7916-8119 Sentence denotes Thus, for a therapeutic application, they should be injected at different time points, ensuring that the local concentration is therapeutically relevant to prevent the virus from invading the host cells.
T275 8120-8222 Sentence denotes In addition, glycofullerenes can be internalized into host cells losing their viral “shield” activity.
T276 8223-8358 Sentence denotes On the other hand, the well-developed surface chemistry of glycofullerenes can be used for other key receptors involved in viral entry.
T277 8359-8558 Sentence denotes For instance, in the case of the current SARS-Cov-2 pandemic, a similar click chemistry strategy can be used to anchor ligands recognized by human lung ACE2 receptors and so inhibiting viral entry.73