Enantioselective Antiviral Activities of Chiral Zinc Oxide Nanoparticles.

Chiral nanoparticles (C-NPs) play a crucial role in biomedical applications, especially in their biological effects on cytotoxicity and metabolism. However, there are rare reports about the antivirus property of C-NPs and their working mechanism. Here, three different types of chiral ZnO NPs (l-ZnO, d-ZnO, and dl-ZnO) were prepared as enantioselective antivirals. Biocompatibility test results showed that the three different chiral ZnO NPs varied significantly in cytotoxicity. Evaluation of their effects against porcine reproductive and respiratory syndrome virus (PRRSV) indicated that compared with d-ZnO and dl-ZnO NPs, l-ZnO NPs exhibited stronger anti-PRRSV activity due to their higher cognate cell adhesion and uptake. Furthermore, the high concentration of l-ZnO NPs can obviously reduce cellular reactive oxygen species (ROS) in MARC-145 cells, thus effectively preventing PRRSV-induced oxidative damage. This study demonstrated the outstanding antiviral properties of l-ZnO NPs, which may facilitate the development and application of C-NPs in antiviral drugs and tissue engineering.

The shape-dependent inhibitory effect of rhein/silver nanocomposites on porcine reproductive and respiratory syndrome virus.

Traditional Chinese medicines (TCMs)/nanopreparations as viral antagonists exhibited a structure-function correlation, i.e., the differences in surface area/volume ratio caused by the variations in shape and size could result in different biochemical properties and biological activities, suggesting an important impact of morphology and structure on the antiviral activity of TCM-based nanoparticles. However, few studies paid attention to this aspect. Here, the effect of TCM-based nanoparticles with different morphologies on their antiviral activity was explored by synthesizing rhein/silver nanocomposites (Rhe@AgNPs) with spherical (S-Rhe/Ag) and linear (L-Rhe/Ag) morphologies, using rhein (an active TCM ingredient) as a reducing agent and taking its self-assembly advantage. Using porcine reproductive and respiratory syndrome virus (PRRSV) as a model virus, the inhibitory effects of S-Rhe/Ag and L-Rhe/Ag on PRRSV were compared. Results showed that the product morphology could be regulated by varying pH values, and both S- and L-Rhe/Ag exhibited good dispersion and stability, but with a smaller size for L-Rhe/Ag. Antiviral experiments revealed that Rhe@AgNPs could effectively inhibit PRRSV infection, but the antiviral effect was morphology-dependent. Compared with L-Rhe/Ag, S-Rhe/Ag could more effectively inactivate PRRSV in vitro and antagonize its adsorption, invasion, replication, and release stages. Mechanistic studies indicated that Rhe@AgNPs could reduce the production of reactive oxygen species (ROS) induced by PRRSV infection, and S-Rhe/Ag also had stronger ROS inhibitory effect. This work confirmed the inhibitory effect of Rhe@AgNPs with different morphologies on PRRSV and provided useful information for treating PRRSV infection with metal nanoparticles synthesized from TCM ingredients.

Application of Oxygen-Group-Based Amorphous Nanomaterials in Electrocatalytic Water Splitting.

Environmentally friendly energy sources (e.g., hydrogen) require an urgent development targeting to address the problem of energy scarcity. Electrocatalytic water splitting is being explored as a convenient catalytic reaction in this context, and promising amorphous nanomaterials (ANMs) are receiving increasing attention due to their excellent catalytic properties.Oxygen group-based amorphous nanomaterials (O-ANMs) are an important component of the broad family of ANMs due to their unique amorphous structure, large number of defects, and abundant randomly oriented bonds, O-ANMs induce the generation of a larger number of active sites, which favors a better catalytic activity. Meanwhile, amorphous materials can disrupt the inherent features of conventional crystalline materials regarding electron transfer paths, resulting in higher flexibility. O-ANMs mainly include VIA elements such as oxygen, sulfur, selenium, tellurium, and other transition metals, most of which are reported to be free of noble metals and have comparable performance to commercial catalysts Pt/C or IrO2 and RuO2 in electrocatalysis. This review covers the features and reaction mechanism of O-ANMs, the synthesis strategies to prepare O-ANMs, as well as the application of O-ANMs in electrocatalytic water splitting. Last, the challenges and prospective remarks for future development in O-ANMs for electrocatalytic water splitting are concluded.

Sulfur quantum dots as a fluorescent sensor for N-acetyl-beta-D-glucosaminidase detection.

N-acetyl-beta-D-glucosaminidase (NAG) is an important biomarker for early clinical diagnosis of renal disease, suggesting the necessity to develop a fast and sensitive method for its detection. In this paper, we developed a fluorescent sensor based on polyethylene glycol (400) (PEG-400)-modified and H2O2-assisted etched sulfur quantum dots (SQDs). According to the fluorescence inner filter effect (IFE), the fluorescence of SQDs can be quenched by the p-nitrophenol (PNP) generated by NAG-catalyzed hydrolysis of p-Nitrophenyl-N-acetyl-ß-D-glucosaminide (PNP-NAG). We successfully used the SQDs as a nano-fluorescent probe to detect the NAG activity from 0.4 to 7.5 U·L-1, with a detection limit of 0.1 U·L-1. Furthermore, the method is highly selective and was successfully used in the detection of NAG activity in bovine serum samples, suggesting its great application prospect in clinical detection.

A fluorescence sensor for thiram detection based on DNA-templated silver nanoclusters without metal ion-mediator.

In this work, we firstly found a strong competitive interaction between thiram and silver atoms of DNA-templated silver nanoclusters (DNA-AgNCs), leading to fluorescence quenching of DNA-AgNCs without additional metal ion-mediator. Furthermore, this thiram-induced fluorescence quenching phenomenon was used to develop a sensor for thiram detection. This fluorescence sensor exhibited good linearity with thiram concentration from 0.20 to 2.0 µM and 0.012-0.20 µM under optimized conditions, with a low detection limit of 0.2 µM and 0.01 µM, respectively. Moreover, this sensor showed superior selectivity towards thiram, and its practicability was verified in apples and soil. This study provides a convenient and rapid "mix and detect" approach for thiram detection within 10 min, suggesting its potential for rapid on-site evaluation of thiram in real samples.

Inner filter effect-based red-shift and fluorescence dual-sensor platforms with sulfur quantum dots for detection and bioimaging of alkaline phosphatase.

Alkaline phosphatase (ALP), one of the vital biomarkers in several diseases, plays a role in indicating disease presence or severity in early diagnosis. Here, a simple H2O2 assisted top-down method was used to synthesize sulfur quantum dots (SQDs) with excitation and emission at 355 nm and 440 nm. Adding ALP into p-nitrophenyl phosphate (p-NPP) and SQDs was found to exhibit a red shift in the emission wavelength and fluorescence intensity quenching of SQDs, respectively, allowing us to propose dual-sensor platforms of red shift of emission wavelength (RSEW) and fluorescence quenching of SQDs. These dual-sensor platforms were highly sensitive and selective in ALP detection, with a linear response to ALP in the concentration range of 0.25 to 100 U L-1 and detection limits of 0.08 and 0.10 U L-1, respectively. The absorption of p-NP at 400 nm showed a good overlap with the excitation and emission of SQDs, leading to inner filter effect-based RSEW and fluorescence quenching of SQDs. This sensor platform was successfully applied in ALP sensing of serum samples as well as monitoring of ALP in cells. More importantly, this platform can serve as an example of using RSEW to detect ALP.

Antiviral Effects of Heparan Sulfate Analogue-Modified Two-Dimensional MXene Nanocomposites on PRRSV and SARS-CoV-2.

Due to the worldwide impact of viruses such as SARS-CoV-2, researchers have paid extensive attention to antiviral reagents against viruses. Despite extensive research on two-dimensional (2D) transition metal carbides (MXenes) in the field of biomaterials, their antiviral effects have received little attention. In this work, heparan sulfate analogue (sodium 3-mercapto-1-propanesulfonate, MPS) modified 2D MXene nanocomposites (Ti3C2-Au-MPS) for prevention of viral infection are prepared and investigated using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus and porcine reproductive and respiratory syndrome virus (PRRSV) as two model viruses. Ti3C2-Au-MPS nanocomposites are shown to possess antiviral properties in the different stages of PRRSV proliferation, such as direct interaction with PRRS virions and inhibiting their adsorption and penetration in the host cell. Additionally, Ti3C2-Au-MPS nanocomposites can strongly inhibit the infection of SARS-CoV-2 pseudovirus as shown by the contents of its reporter gene GFP and luciferase. These results demonstrate the potential broad-spectrum antiviral property of Ti3C2-Au-MPS nanocomposites against viruses with the receptor of heparin sulfate. This work sheds light on the specific antiviral effects of MXene-based nanocomposites against viruses and may facilitate further exploration of their antiviral applications.

Research Update of Emergent Sulfur Quantum Dots in Synthesis and Sensing/Bioimaging Applications.

Due to their unique optical property, low toxicity, high hydrophilicity, and low cost, sulfur quantum dots (SQDs), an emerging luminescent nanomaterial, have shown great potential in various application fields, such as sensing, bioimaging, light emitting diode, catalysis, and anti-bacteria. This minireview updates the synthetic methods and sensing/bioimaging applications of SQDs in the last few years, followed by discussion of the potential challenges and prospects in their synthesis and sensing/bioimaging applications, with the purpose to provide some useful information for researchers in this field.

Inhibitory effect and mechanism of gelatin stabilized ferrous sulfide nanoparticles on porcine reproductive and respiratory syndrome virus.

BACKGROUND: The infection and spread of porcine reproductive and respiratory syndrome virus (PRRSV) pose a serious threat to the global pig industry, and inhibiting the viral infection process is a promising treatment strategy. Nanomaterials can interact with viruses and have attracted much attention due to their large specific surface area and unique physicochemical properties. Ferrous sulfide nanoparticles (FeS NPs) with the characteristics of high reactivity, large specific surface area, and low cost are widely applied to environmental remediation, catalysis, energy storage and medicine. However, there is no report on the application of FeS NPs in the antiviral field. In this study, gelatin stabilized FeS nanoparticles (Gel-FeS NPs) were large-scale synthesized rapidly by the one-pot method of co-precipitation of Fe2+ and S2‒. RESULTS: The prepared Gel-FeS NPs exhibited good stability and dispersibility with an average diameter of 47.3 nm. Additionally, they were characterized with good biocompatibility and high antiviral activity against PRRSV proliferation in the stages of adsorption, invasion, and replication. CONCLUSIONS: We reported for the first time the virucidal and antiviral activity of Gel-FeS NPs. The synthesized Gel-FeS NPs exhibited good dispersibility and biocompatibility as well as effective inhibition on PRRSV proliferation. Moreover, the Fe2+ released from degraded Gel-FeS NPs still displayed an antiviral effect, demonstrating the advantage of Gel-FeS NPs as an antiviral nanomaterial compared to other nanomaterials. This work highlighted the antiviral effect of Gel-FeS NPs and provided a new strategy for ferrous-based nanoparticles against PRRSV.

Simple and rapid colorimetric visualization of tetramethylthiuram disulfide (thiram) sensing based on anti-aggregation of gold nanoparticles.

Thiram is widely used in agriculture and can pose high toxicity to humans through food and soil contamination, suggesting the necessity to develop a method for convenient and rapid detection of thiram residues. Herein, we synthesized gold nanoparticles (Au NPs) encoded with 4-aminothiophenol (4-ABT) (Au NPs@4-ABT), whose aggregation process can be triggered by silver ions (Ag+), but can also be specifically inhibited by the competitive reaction between thiram and Ag+. By monitoring the color change of Au NPs@4-ABT probe, the thiram concentration can be detected within 15 min with detection limit of 0.04 µM over a linear range of 0.05-2.0 µM. This visualization method has the advantages of good sensitivity and specificity, simple operation, rapid detection, and not requiring any large instrument or sophisticated design, and its practicability has also been verified in apple and soil, indicating its great potential for on-site evaluation of thiram in real samples.

Mesoporous MnFe2O4 magnetic nanoparticles as a peroxidase mimic for the colorimetric detection of urine glucose.

Mesoporous MnFe2O4 magnetic nanoparticles (mMnFe2O4 MNPs) were prepared with a one-step synthesis method and characterized to possess intrinsic peroxidase-like activity, and had obvious advantages over other peroxidase nanozymes in terms of high catalytic affinity, high stability, mono-dispersion, easy preparation, and quick separation. The mMnFe2O4 MNPs were used as a colorimetric sensor for indirect sensing of urine glucose based on the sensing principle that H2O2 can be produced from glucose oxidation catalyzed by glucose oxidase (GOx), and under the catalysis of the mMnFe2O4 MNPs nanozyme, H2O2 can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue color in a few minutes. This sensor is simple, cheap, sensitive, and specific to glucose detection with a detection limit of 0.7 µM, suggesting its potential for on-site glucose detection.

A ratiometric fluorescent probe for pH detection based on Ag2S quantum dots-carbon dots nanohybrids.

In this study, a novel ratiometric fluorescent nanoprobe for pH monitoring has been developed by synthesizing red fluorescent Ag2S quantum dots (Ag2S QDs) and green fluorescent carbon dots (CDs) nanohybrids (Ag2S CDs) in one pot using CDs as templates. The nanoprobe exhibits dual-emission peaks at 500 and 670 nm under a single-excitation wavelength of 450 nm. The red fluorescence can be selectively quenched by increasing pH, while the green fluorescence is an internal reference. Therefore, the change of the relative fluorescence intensity (I500/I670) in the ratiometric Ag2S CDs probes can be used for pH sensing. The results revealed that I500/I670 of Ag2S CDs probes was linearly related to pH variation between pH 5.4 and 6.8. Meanwhile, the Ag2S CDs probes possessed a good reversibility along with pH changing between 5.0 and 7.0 without any interruption from common metal ions, proteins and other interferences.

An overview of functional nanoparticles as novel emerging antiviral therapeutic agents.

Research on highly effective antiviral drugs is essential for preventing the spread of infections and reducing losses. Recently, many functional nanoparticles have been shown to possess remarkable antiviral ability, such as quantum dots, gold and silver nanoparticles, nanoclusters, carbon dots, graphene oxide, silicon materials, polymers and dendrimers. Despite their difference in antiviral mechanism and inhibition efficacy, these functional nanoparticles-based structures have unique features as potential antiviral candidates. In this topical review, we highlight the antiviral efficacy and mechanism of these nanoparticles. Specifically, we introduce various methods for analyzing the viricidal activity of functional nanoparticles and the latest advances in antiviral functional nanoparticles. Furthermore, we systematically describe the advantages and disadvantages of these functional nanoparticles in viricidal applications. Finally, we discuss the challenges and prospects of antiviral nanostructures. This topic review covers 132 papers and will enrich our knowledge about the antiviral efficacy and mechanism of various functional nanoparticles.

Glycyrrhizic-Acid-Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms.

With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly-CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly-CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly-CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics analysis demonstrates that Gly-CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly-CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly-CDs. The integrated results demonstrate that Gly-CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection.

High antiviral activity of mercaptoethane sulfonate functionalized Te/BSA nanostars against arterivirus and coronavirus.

Heparan sulfate (HS) is a kind of cellular adhesion receptor that mediates the attachment and internalization of virus infection. Herein, to mimic the cell surface receptor, mercaptoethane sulfonate (MES), an analogue of HS, was used as the surface modifier to synthesize bovine serum albumin (BSA)-coated tellurium nanoparticles (Te/BSA NPs) with a unique triangular star shape (Te/BSA nanostars). Using porcine reproductive and respiratory syndrome virus (PRRSV), which utilizes HS as a cellular receptor, as a model of arterivirus, we found that Te/BSA nanostars suppressed virus infection mainly by inhibiting the virus internalization process. Interestingly, Te/BSA nanostars exhibited much higher antiviral activity than the spherical Te/BSA NPs (Te/BSA nanospheres), the Te/BSA NPs were synthesized with GSH as a substitute of MES, suggesting that both MES modification and the novel shapes of Te/BSA NPs enhance their antiviral activity. Finally, the antiviral effect of Te/BSA nanostars on porcine epidemic diarrhea virus (PEDV), a model of coronavirus, was also demonstrated, indicating the potential broad-spectrum antiviral property of Te/BSA nanostars.

GSH-ZnS Nanoparticles Exhibit High-Efficiency and Broad-Spectrum Antiviral Activities via Multistep Inhibition Mechanisms.

Despite the good biocompatibility and antibacterial activity of zinc sulfide nanoparticles (ZnS NPs), whether they possess antiviral activity is still unclear. Here, GSH-modified ZnS NPs (GSH-ZnS NPs) were synthesized and their significant antiviral activity was demonstrated using the Arteriviridae family RNA virus, porcine reproductive and respiratory syndrome virus (PRRSV), as a model. Mechanistically, GSH-ZnS NPs were shown to reduce PRRSV-induced ROS production to prevent PRRSV multiplication, with no activating effect on the interferon (IFN) signal pathway, the first defense line against virus infection. Furthermore, isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis of GSH-ZnS NP-treated cells revealed the involvement of numerous crucial proteins in virus proliferation, with vitronectin (VTN) being confirmed as an efficient PRRSV antagonist here. Furthermore, GSH-ZnS NPs were found to have potent antiviral effects on the Herpesviridae family DNA virus, pseudorabies virus (PRV), the Coronaviridae family positive-sense RNA virus, porcine epidemic diarrhea virus (PEDV), and the Rhabdoviridae family negative-stranded RNA virus, vesicular stomatitis virus (VSV), indicating their broad-spectrum antiviral activity against viruses from different families with various genome types. Overall, GSH-ZnS NP is a prospective candidate for the development of antiviral nanomaterials and may serve as a model for investigation of potential host restriction factors in combination with proteomics.

N-doped carbon dots under Xenon lamp irradiation: Fluorescence red-shift and its potential mechanism.

Despite extensive research on carbon dots (CDs), rare studies have been performed on the photostability of CDs. Here, the photostability of CDs synthesized with 3-aminobenzoic acid were systematically investigated under different pH conditions (5.0, 7.4 and 9.0). The results showed that under Xenon lamp irradiation, the fluorescence (FL) intensity of the CDs exhibited an increase first and then a decrease, with a gradual shift of the maximum emission wavelength to longer wavelength. Further investigation indicated that the irradiation induced the change of the CD surface functional groups and gave rise to aggregation, resulting in the formation of larger particles. This study provided important reference value towards research on CDs properties.

A novel gold-nanocluster-based fluorescent sensor for detection of sodium 2-mercaptoethanesulfonate.

Gold nanoclusters (Au NCs) are widely used in various types of detections due to their unique fluorescence properties. However, there are rare reports on enhanced fluorescence sensors for drug molecules. Here, we report a novel strategy for detection of sodium 2-mercaptoethanesulfonate (MES) by using a fluorescence-enhanced histidine stabilized Au NCs (His-Au NCs) probe. This fluorescence probe showed excellent selectivity and sensitivity towards MES. Furthermore, we have demonstrated that the fluorescence enhancement of His-Au NCs was attributed to ligand exchange with MES by Fourier Transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The feasibility of practical applications of this probe was further investigated by sensing the MES content in Mesna injection (Uromitexan).

Tellurium/Bovine Serum Albumin Nanocomposites Inducing the Formation of Stress Granules in a Protein Kinase R-Dependent Manner.

The effect of nanoparticles (NPs) on cellular stress responses is important to the understanding of nanotoxicities and developing safe therapies. Although the relationship between NPs and cellular stress responses has been preliminarily investigated, stress responses to NPs remain unclear. Here, tellurium/bovine serum albumin (Te/BSA) nanocomposites were prepared using sodium tellurite, BSA, and glutathione as precursors. The as-prepared Te/BSA nanocomposites, with particle size similar to that of many viruses, are found to induce the formation of stress granules (SGs), a kind of cytoplasmic RNA granule formed under various stresses. The SGs in Te/BSA nanocomposite-treated cells are composed of T-cell internal antigen 1 (TIA1), TIA1-related protein, and eukaryotic initiation factor 3η. Using chemical inhibitors and small interfering RNA-mediated silencing, protein kinase R (PKR) is identified as the α-subunit of eukaryotic initiation factor 2 (eIF2α)-kinase activated upon Te/BSA nanocomposite incubation, which is also the dominant kinase responsible for eIF2α activation under virus infection. Mechanistically, PKR is activated in a heparin-dependent manner. This study reveals a biological effect of Te/BSA nanocomposites on stress responses, providing a preliminary basis for further research on viruslike particles and the application of NPs in biology.

Glutathione-Capped Ag2S Nanoclusters Inhibit Coronavirus Proliferation through Blockage of Viral RNA Synthesis and Budding.

Development of novel antiviral reagents is of great importance for the control of virus spread. Here, Ag2S nanoclusters (NCs) were proved for the first time to possess highly efficient antiviral activity by using porcine epidemic diarrhea virus (PEDV) as a model of coronavirus. Analyses of virus titers showed that Ag2S NCs significantly suppressed the infection of PEDV by about 3 orders of magnitude at the noncytotoxic concentration at 12 h postinfection, which was further confirmed by the expression of viral proteins. Mechanism investigations indicated that Ag2S NCs treatment inhibits the synthesis of viral negative-strand RNA and viral budding. Ag2S NCs treatment was also found to positively regulate the generation of IFN-stimulating genes (ISGs) and the expression of proinflammation cytokines, which might prevent PEDV infection. This study suggest the novel underlying of Ag2S NCs as a promising therapeutic drug for coronavirus.