PMC:7376974 / 59768-69544 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T385 0-31 Sentence denotes Nanomaterials for Drug Delivery
T386 32-102 Sentence denotes Different HNMs have been widely tested for drug delivery applications.
T387 103-238 Sentence denotes The advantages of this strategy are several including enhance drug solubility and the possibility of targeting and multivalent effects.
T388 239-418 Sentence denotes As a potential broad spectral antiviral agent, AgNPs can prevent the virus from adsorbing to the host cell in the early stage of infection and thus show strong antiviral activity.
T389 419-521 Sentence denotes After the cells are infected by the virus, there are ways to inhibit cell apoptosis (Figure 2, right).
T390 522-840 Sentence denotes For example, Lv et al. studied the anti-TGEV activity of AgNPs in swine testicle cells and explored the possible mechanism of AgNP inhibition of TGEV infection-induced apoptosis.18 The results showed that these AgNPs are able to decrease cell apoptosis through the activation of p38/mitochondria-caspase-3 signaling.18
T391 841-1098 Sentence denotes Although the use of AgNPs has shown good antiviral action to further improve the therapeutic effects and reduce both side effects and drug resistance, the way of binding drugs or genes and other therapeutic agents to AgNPs has received particular attention.
T392 1099-1255 Sentence denotes It has been observed that AgNPs inhibit the activities of neuraminidase and hemagglutinin, preventing the H1N1 influenza virus from attaching to host cells.
T393 1256-1384 Sentence denotes At the same time, the potential molecular mechanisms revealed that caspase-3-mediated apoptosis was inhibited by ROS generation.
T394 1385-1443 Sentence denotes AgNPs modified with polyethylenimine (PEI) can bind siRNA.
T395 1444-1749 Sentence denotes Ag@PEI@siRNA exhibited superior abilities for enhanced cellular uptake and blocking EV71 virus infection and significantly decreased the apoptotic cell population, which prevented the spread of EV71 virus.37 In addition to drugs and siRNA, neutralizing antibodies in combination with AgNPs were developed.
T396 1750-1904 Sentence denotes The results demonstrated that there is an additive effect between the antibody and AgNPs when combined against cell-associated HIV-1 infection in vitro.96
T397 1905-1971 Sentence denotes The membranotropic properties of fullerenes were widely exploited.
T398 1972-2315 Sentence denotes For example, pristine C60, after accumulation at the cell membrane, can translocate into the cytoplasm by crossing the membrane through multiple energy-dependent pathways despite its hydrophobic character.97 Fullerenes can be made water dispersible using surfactants, sonication or first dissolving them in appropriate organic solvents (DMSO).
T399 2316-2553 Sentence denotes The use of fullerenes as inhibitors of viruses started in 1993 with a study focused on HIV infection.98 This work revealed the interaction between C60 derivatives and HIV protease through molecular modeling and experimental verification.
T400 2554-2689 Sentence denotes HIV protease (HIV-PR) is involved in the mechanism of replication in the maturation of HIV virion, cleaving newly synthesized proteins.
T401 2690-2958 Sentence denotes The active site of HIV protease has a cavity of 10 Å closed to the diameter of C60 cage.99 Molecular docking and experiments on HIV-PR catalytic activity revealed a blockage of the active site of the enzyme by van der Waals interactions leading to an antiviral effect.
T402 2959-3122 Sentence denotes The following studies were based on a structure–activity relationship between functionalized fullerenes and HIV-PR with the aim to increase the antiviral activity.
T403 3123-3538 Sentence denotes The introduction of pyrrolidinium salts onto C60 was tested against the activity of HIV-1 strain.100 In a second study, C60 bearing two ammonium groups was applied against the activity of HIV-1 and HIV-2 strains.101 The results showed the importance of having two moieties in a precise position on the fullerene cage and the influence of the charge of the different salts sensibly increasing its antiviral activity.
T404 3539-3641 Sentence denotes Further investigations using different functional groups (e.g., amino acid derivatives) were explored.
T405 3642-3959 Sentence denotes C60 functionalized with aminobutyric acid and aminocaproic acid was able to inhibit HIV viral replication at subnanomolar concentrations.63 In another work, anionic and cationic pyrrolidinium salts and amino acid functionalized fullerene derivatives were used for the inhibition of HIV reverse transcriptase (HIV-RT).
T406 3960-4325 Sentence denotes Fullerene compounds were compared to nevirapine, an available drug against HIV-RT, revealing a better inhibition compared to the pure drug.102 The antiviral property of carboxylated fullerenes was confirmed by another study.103 Results obtained in vitro on CEM cell line showed low toxicity and a submicromolar EC50 against HIV-1 and HIV-2 strain viral replication.
T407 4326-4409 Sentence denotes Several mechanisms of HIV protease inhibitors have been hypothesized and simulated.
T408 4410-4663 Sentence denotes Some studies investigated the action of fullerene derivatives on viral replication cycle and the virus maturation (Figure 11).98,104 For the latter, it was suggested an impairment due to a strong interaction between fullerene and the immature capsid.105
T409 4664-4743 Sentence denotes Figure 11 Illustration of fullerene affecting the viral replication mechanism.
T410 4744-4870 Sentence denotes Interaction between fullerene and viral protein blocking either the transcription or the translation in the viral replication.
T411 4871-5214 Sentence denotes Other RNA viruses share ways of viral replication similar to HIV.106 C60 functionalized with an amino acid derivative was investigated against Hepatitis C RNA polymerase (HCV-RP).102 This essential enzyme for viral replication was inhibited in a submicromolar range, similarly to benzo-1,2,4-thiadiazine, a potent specific inhibitor of HCV-RP.
T412 5215-5505 Sentence denotes Another publication highlighted the effect of a C70 poly(carboxylic acid) derivative on different strains of influenza virus (e.g., A, H1N1, H3N2, and B).107 The inhibition was comparable to Tamiflu, rimantadine, ribavirin, and amantadine, but the mechanism of action remains still unclear.
T413 5506-5620 Sentence denotes These data emphasize that fullerenes C60 or C70 can be potent universal antiviral drugs for RNA enveloped viruses.
T414 5621-5723 Sentence denotes However, clear elucidations of the mechanisms of action and in vivo studies are still a missing point.
T415 5724-5982 Sentence denotes Due to their high surface/weight ratio and capacity to pass through cell membranes, carbon nanotubes (CNTs) have been extensively explored for drug and gene delivery applications.108 CNTs have been also successfully used for the delivery of antiviral agents.
T416 5983-6232 Sentence denotes Compared to pristine materials, oxidized CNTs (ox-CNTs) showed an inhibitory activity for HIV viruses per se.109 This effect has been associated with the oxygenated groups that increase the hydrophilicity and the colloidal stability of the material.
T417 6233-6421 Sentence denotes The antiviral efficiency has been correlated to the ox-CNT interaction with host cells.109 However, it is not clear how and what kind of mechanism blocks the viral machinery in host cells.
T418 6422-6513 Sentence denotes Different anchoring strategies have been explored to link antiviral drugs onto CNT surface.
T419 6514-7156 Sentence denotes For instance, ox-CNTs were covalently linked to 2-amino-3-nitro-1-(3,5-dimethylbenzyl)-aniline (CHI360) and N-(2-aminophenyl-3-nitro-)-3,5-dimethylbenzenesulfonamide (CHI415), two active non-nucleoside reverse transcriptase inhibitors for HIV treatment.109 Following the covalent conjugation, only a moderate antiviral effect was observed compared to pure drugs, indicating that most probably the NM cell trafficking played a key role on the virucidal activity.109 In another study, ox-CNTs functionalized with cyclodextrin were used for the delivery of acyclovir (a prodrug inhibitor of the viral DNA polymerases) for the treatment of HSV-1.
T420 7157-7458 Sentence denotes Preliminary results showed that when acyclovir was delivered via the nanotubes, the viral antireplicative effect was higher than the free drug.110 More recently, a similar approach was applied to herpes virus using cyclodextrin and PEI-functionalized CNTs for co-delivery of cidofovir and plasmid DNA.
T421 7459-7873 Sentence denotes However, the antiviral effect of the materials was not explained, and the transfection effect was not satisfactory.111 Functionalized CNTs have been also used for delivery of ribavirin in vivo using grass carp as an animal model for the study of grass carp reovirus. ox-CNTs were first functionalized via amidation with BSA, and then ribavirin was covalently bound to the protein via esterification (Figure 12).112
T422 7874-7975 Sentence denotes Figure 12 Schematic procedure of the functionalization of single-walled CNTs (SWCNTs) and ribavirin.
T423 7976-8018 Sentence denotes Reproduced with permission from ref (112).
T424 8019-8048 Sentence denotes Copyright 2015, Elsevier B.V.
T425 8049-8270 Sentence denotes In vivo tests demonstrated that, when ribovirin was shuttled by ox-CNTs, the antiviral efficiency was significantly increased without any evident toxicity and no significant changes in ROS-generating enzymatic activities.
T426 8271-8338 Sentence denotes The use of CNTs in drug delivery is however still controversial.113
T427 8339-8428 Sentence denotes Graphene-based materials have been limitedly studied as antiviral drug delivery carriers.
T428 8429-8480 Sentence denotes Only a few examples can be found in the literature.
T429 8481-8730 Sentence denotes Graphene quantum dots (GQDs) were used for drug delivery of CHI360 and CHI415 and tested in vitro against HIV similarly to CNTs.109 Both the prepared GQD-CHI360 and GQD-CHI415 showed a high antiviral activity once into host cells, with low toxicity.
T430 8731-8844 Sentence denotes GO has been also used for the delivery of DNAzyme into hepatic cells allowing to block the hepatitis C infection.
T431 8845-8946 Sentence denotes This specific DNA single strand is able to recognize the viral mRNA and to silence its expression.114
T432 8947-9021 Sentence denotes Overall, carbon NMs proved to be interesting carriers for antiviral drugs.
T433 9022-9122 Sentence denotes However, several questions need to be answered before their safe application as antiviral materials.
T434 9123-9368 Sentence denotes Different reports have demonstrated that pristine CNTs display relevant toxicity for healthy cells, but by oxidation of the tubes, the side effects can be sensibly reduced.109 In addition, more investigations should be performed on CNT toxicity.
T435 9369-9652 Sentence denotes These nanocarriers indeed are not “innocent delivery agents”, but they play a key role in drug internalization pathway and in host cell machinery that might be averse to the expected therapeutic effects.109 So far, CNT application in biological systems has been studied for 20 years.
T436 9653-9776 Sentence denotes However, due to their possible toxicity, their real application in clinics seems to be steeper and difficult to achieve.112