PMC:7376974 / 24303-30401 JSONTXT 10 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T160 0-18 Sentence denotes Gold Nanoparticles
T161 19-249 Sentence denotes Compared to AgNPs, AuNPs exhibit reduced toxicity on healthy cells, making them more attractive for in vivo and clinical applications.38 Indeed, AuNPs have been successfully tested as inhibitors of viral entry into the host cells.
T162 250-447 Sentence denotes AuNPs interact with hemagglutinin (HA), where Au is able to oxidize the disulfide bond of this glycoprotein causing its inactivation, thus impeding the membrane fusion of the virus with host cells.
T163 448-909 Sentence denotes Targeting HA has emerged as an alternative strategy to the actual therapies (e.g., matrix protein 2 and neuramidase), especially to pandemic viruses that show an accelerated mutation speed of their surface proteins, hence a resistance to conventional treatments increasing their infectivity and mortality.38 This strategy has been applied to influenza (e.g., H1N1, HCV) and herpes viruses.39−44 The activity of AuNPs is proportional to the surface area exposed.
T164 910-1027 Sentence denotes As a consequence, the size and the morphology of these metal NPs play a substantial role in their antiviral activity.
T165 1028-1346 Sentence denotes Recently, Kim et al. have reported that porous AuNPs are able to inhibit influenza A infection more efficiently than nonporous AuNPs.39 This effect has been associated with the higher surface area of the porous material that favors their interaction with capsids and thus increases their antiviral activity (Figure 4).
T166 1347-1456 Sentence denotes Figure 4 Schematic illustration of inactivation of influenza A virus (IAV) treated with porous AuNP (PoGNP).
T167 1457-1533 Sentence denotes PoGNP interacts with IAV surface proteins and cleaves their disulfide bonds.
T168 1534-1589 Sentence denotes Inactivated viruses exhibit lower infectivity to cells.
T169 1590-1670 Sentence denotes Reproduced with permission under a Creative Commons CC-BY license from ref (39).
T170 1671-1723 Sentence denotes Copyright 2020 BioMed Central Ltd., Springer Nature.
T171 1724-1865 Sentence denotes Besides the per se antiviral activity, AuNP surface modifications have been developed in order to enhance their overall therapeutic benefits.
T172 1866-1984 Sentence denotes The engineering of tailored AuNPs with selected ligands has allowed the preparation of efficient antiviral nanoagents.
T173 1985-2115 Sentence denotes The target ligands can be introduced directly during the particle synthesis via ligand exchange reactions or ligand modifications.
T174 2116-2603 Sentence denotes For instance, direct reduction of gold ions in the presence of gallic acid produced homogeneous AuNPs able to sensibly reduce herpes simplex virus infection in vitro.40 Compared to free ligand NPs, functionalized AuNPs benefit from the multivalency effect and higher circulation times, decreasing the needed therapeutic concentrations.39 Functionalized AuNPs can present organic groups that mimic host cell surfaces or other specific molecular patterns that selectively target the virus.
T175 2604-2726 Sentence denotes Normally, negative charges are used to mimic cell surfaces and favor the interaction between the particles and the capsid.
T176 2727-3218 Sentence denotes In particular, sulfonates and organic sulfates have been used for their capacity to attract the virus via capsid protein interaction and block the HA activity.41 AuNPs functionalized with sulfonates showed an increasing inhibition of influenza A compared to the nanoparticles capped with succinic acid.42 This study also demonstrated that there is not a correlation between the negative charge and the antiviral activity, but instead the inhibition depends mainly on the organic groups used.
T177 3219-3407 Sentence denotes Thiol-capped AuNPs also displayed powerful inactivation of bovine viral diarrhea virus in vitro.43 Multivalency has been exploited in more complex systems using dendrons as capping agents.
T178 3408-3590 Sentence denotes This strategy allows to generate higher concentrations of the target ligand in close proximity to the AuNPs and to increase the binding efficiency of the nanoparticles to the capsid.
T179 3591-3707 Sentence denotes The driving force of the antiviral efficiency relies on the concentration of the targeting agent onto the particles.
T180 3708-3885 Sentence denotes Sulfonated dendrons were grafted to AuNPs via a sulfide bond and tested for HIV inhibition.44 The results showed that the decorated AuNPs exerted a higher affinity to the virus.
T181 3886-4126 Sentence denotes Additionally, comparing AuNPs functionalized with different generation dendrons, those with a third generation displayed the highest inhibition performance with an IC50 below 0.1 μmol/mL, thus making them attractive for in vivo translation.
T182 4127-4593 Sentence denotes It is worth noting that the inhibition efficiency is strictly dependent on the available sulfonate groups present on the surface of the NPs, making crucial a thorough characterization of the material.44 The size of the AuNPs clearly plays an important role in the concentration of targeting ligands exposed per particle.45 Indeed, too big NPs have a limited surface area, while too small would not allow an efficient grafting of the dendrons due to steric hindrance.
T183 4594-4792 Sentence denotes For instance, it has been shown that dendron-functionalized AuNPs showed a size-dependent antiviral activity for influenza virus, where 14 nm particles exhibited a higher efficiency than 2 nm AuNPs.
T184 4793-4969 Sentence denotes This has been associated with the low functionalization grade of the small nanoparticles and to the inappropriate spatial distribution of the interacting ligand/receptor pairs.
T185 4970-5075 Sentence denotes The development of viral proteomics has profoundly transformed the antiviral and disinfection strategies.
T186 5076-5197 Sentence denotes In particular, small molecules and peptides able to target and block the viral biochemical machinery have been developed.
T187 5198-5379 Sentence denotes However, despite these efforts into the drug design, many of these molecules suffer from poor biological effect, low concentration in the diseased areas, and undesired side effects.
T188 5380-5522 Sentence denotes In this context, AuNPs have been coupled to biologically inactive small molecules to create biologically active multivalent AuNP therapeutics.
T189 5523-5821 Sentence denotes A bright example has been reported by Bowman et al., where the authors functionalized AuNPs with SDC-1721, a small membrane fusion inhibitor of HIV.46 The results demonstrated that, while pure SDC-1721 has low activity, functionalized AuNPs are able to inhibit HIV replication at μM concentrations.
T190 5822-5882 Sentence denotes Similar results have been reported using targeting peptides.
T191 5883-6098 Sentence denotes In particular, it was evidenced that the functionalized AuNPs can sensibly reduce the IC50 up to 2 orders of magnitude compared to pure peptides.47 Preliminary results in vivo confirmed the biosafety of the AuNPs.48