Highin vitroactivity of gold and silver nanoparticles from Solanum mammosum L. against SARS-CoV-2 surrogate Phi6 and viral model PhiX174.

The search for new strategies to curb the spread of the SARS-CoV-2 coronavirus, which causes COVID-19, has become a global priority. Various nanomaterials have been proposed as ideal candidates to inactivate the virus; however, because of the high level of biosecurity required for their use, alternative models should be determined. This study aimed to compare the effects of two types of nanomaterials gold (AuNPs) and silver nanoparticles (AgNPs), recognized for their antiviral activity and affinity with the coronavirus spike protein using PhiX174 and enveloped Phi6 bacteriophages as models. To reduce the toxicity of nanoparticles, a species known for its intermediate antiviral activity,Solanum mammosumL. (Sm), was used. NPs prepared with sodium borohydride (NaBH4) functioned as the control. Antiviral activity against PhiX174 and Phi6 was analyzed using its seed, fruit, leaves, and essential oil; the leaves were the most effective on Phi6. Using the aqueous extract of the leaves, AuNPs-Sm of 5.34 ± 2.25 nm and AgNPs-Sm of 15.92 ± 8.03 nm, measured by transmission electron microscopy, were obtained. When comparing NPs with precursors, both gold(III) acetate and silver nitrate were more toxic than their respective NPs (99.99% at 1 mg ml-1). The AuNPs-Sm were less toxic, reaching 99.30% viral inactivation at 1 mg ml-1, unlike the AgNPs-Sm, which reached 99.94% at 0.01 mg ml-1. In addition, cell toxicity was tested in human adenocarcinoma alveolar basal epithelial cells (A549) and human foreskin fibroblasts. Gallic acid was the main component identified in the leaf extract using high performance liquid chromatography with diode array detection (HPLC-DAD). The FT-IR spectra showed the presence of a large proportion of polyphenolic compounds, and the antioxidant analysis confirmed the antiradical activity. The control NPs showed less antiviral activity than the AuNPs-Sm and AgNPs-Sm, which was statistically significant; this demonstrates that both theS. mammosumextract and its corresponding NPs have a greater antiviral effect on the surrogate Phi bacteriophage, which is an appropriate model for studying SARS-CoV-2.

Comparative statistical analysis of the release kinetics models for nanoprecipitated drug delivery systems based on poly(lactic-co-glycolic acid).

Poly(lactic-co-glycolic acid) is one of the most used polymers for drug delivery systems (DDSs). It shows excellent biocompatibility, biodegradability, and allows spatio-temporal control of the release of a drug by altering its chemistry. In spite of this, few formulations have reached the market. To characterize and optimize the drug release process, mathematical models offer a good alternative as they allow interpreting and predicting experimental findings, saving time and money. However, there is no general model that describes all types of drug release of polymeric DDSs. This study aims to perform a statistical comparison of several mathematical models commonly used in order to find which of them best describes the drug release profile from PLGA particles synthesized by nanoprecipitation method. For this purpose, 40 datasets extracted from scientific articles published since 2016 were collected. Each set was fitted by the models: order zero to fifth order polynomials, Korsmeyer-Peppas, Weibull and Hyperbolic Tangent Function. Some data sets had few observations that do not allow to apply statistic test, thus bootstrap resampling technique was performed. Statistic evidence showed that Hyperbolic Tangent Function model is the one that best fit most of the data.

Computational Modeling of the Interaction of Silver Clusters with Carbohydrates.

Silver nanoparticles are recognized for their numerous physical, biological, and pharmaceutical applications. In the present study, the interaction of silver clusters with monosaccharide molecules is examined to identify which molecule works better as a reducing agent in the application of a green synthesis approach. Geometry optimization of clusters containing one, three, and five silver atoms is performed along with the optimization of α-d-glucose, α-d-ribose, d-erythrose, and glyceraldehyde using density functional theory. Optimized geometries allow identifying the interaction formed in the silver cluster and monosaccharide complexes. An electron localization function analysis is performed to further analyze the interaction found and explain the reduction process in the formation of silver nanoparticles. The overall results indicate that glyceraldehyde presents the best characteristics to serve as the most efficient reducing agent.

Determination of Antioxidant Activity by Oxygen Radical Absorbance Capacity (ORAC-FL), Cellular Antioxidant Activity (CAA), Electrochemical and Microbiological Analyses of Silver Nanoparticles Using the Aqueous Leaf Extract of Solanum mammosum L.

PURPOSE: The importance of studying polyphenolic compounds as natural antioxidants has encouraged the search for new methods of analysis that are quick and simple. The synthesis of silver nanoparticles (AgNPs) using plant extracts has been presented as an alternative to determine the total polyphenolic content and its antioxidant activity. METHODS: In this study, aqueous leaf extract of Solanum mammosum, a species of plant endemic to South America, was used to produce AgNPs. The technique of oxygen radical absorption capacity using fluorescein (ORAC-FL) was used to measure antioxidant activity. The oxidation of the 2´,7´-dichlorodihydrofluorescein diacetate (DCFH2-DA) as fluorescent probe was used to measure cellular antioxidant activity (CAA). Electrochemical behavior was also examined using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Total polyphenolic content (TPH) was analyzed using the Folin-Ciocalteu method, and the major polyphenolic compound was analyzed by high performance liquid chromatography with diode array detector (HPLC/DAD). Finally, a microbial analysis was conducted using Escherichia coli and Bacillus sp. RESULTS: The average size of nanoparticles was 5.2 ± 2.3 nm measured by high-resolution transmission electron microscopy (HR-TEM). The antioxidant activity measured by ORAC-FL in the extract and nanoparticles were 3944 ± 112 and 637.5 ± 14.8 µM ET/g of sample, respectively. Cellular antioxidant activity was 14.7 ± 0.2 for the aqueous extract and 12.5 ± 0.2 for the nanoparticles. The electrochemical index (EI) was 402 µA/V for the extract and 324 µA/V for the nanoparticles. Total polyphenolic content was 826.6 ± 20.9 and 139.7 ± 20.9 mg EGA/100 g of sample. Gallic acid was the main polyphenolic compound present in the leaf extract. Microbiological analysis revealed that although leaf extract was not toxic for Escherichia coli and Bacillus sp., minor toxic activity for AgNPs was detected for both strains. CONCLUSION: It is concluded that the aqueous extract of the leaves of S. mammosum contains nontoxic antioxidant compounds capable of producing AgNPs. The methods using AgNPs can be used as a fast analytical tool to monitor the presence of water-soluble polyphenolic compounds from plant origin. Analysis and detection of new antioxidants from plant extracts may be potentially applicable in biomedicine.

Fertility and Iron Bioaccumulation in Drosophila melanogaster Fed with Magnetite Nanoparticles Using a Validated Method.

Research on nanomaterial exposure-related health risks is still quite limited; this includes standardizing methods for measuring metals in living organisms. Thus, this study validated an atomic absorption spectrophotometry method to determine fertility and bioaccumulated iron content in Drosophila melanogaster flies after feeding them magnetite nanoparticles (Fe3O4NPs) dosed in a culture medium (100, 250, 500, and 1000 mg kg-1). Some NPs were also coated with chitosan to compare iron assimilation. Considering both accuracy and precision, results showed the method was optimal for concentrations greater than 20 mg L-1. Recovery values were considered optimum within the 95-105% range. Regarding fertility, offspring for each coated and non-coated NPs concentration decreased in relation to the control group. Flies exposed to 100 mg L-1 of coated NPs presented the lowest fertility level and highest bioaccumulation factor. Despite an association between iron bioaccumulation and NPs concentration, the 500 mg L-1 dose of coated and non-coated NPs showed similar iron concentrations to those of the control group. Thus, Drosophila flies' fertility decreased after NPs exposure, while iron bioaccumulation was related to NPs concentration and coating. We determined this method can overcome sample limitations and biological matrix-associated heterogeneity, thus allowing for bioaccumulated iron detection regardless of exposure to coated or non-coated magnetite NPs, meaning this protocol could be applicable with any type of iron NPs.

Novel antimicrobial cruzioseptin peptides extracted from the splendid leaf frog, Cruziohyla calcarifer.

Antimicrobial peptides (AMPs) constitute part of a broad range of bioactive compounds present on diverse organisms, including frogs. Peptides, produced in the granular glands of amphibian skin, constitute a component of their innate immune response, providing protection against pathogenic microorganisms. In this work, two novel cruzioseptins peptides, cruzioseptin-16 and -17, extracted from the splendid leaf frog Cruziohyla calcarifer are presented. These peptides were identified using molecular cloning and tandem mass spectrometry. Later, peptides were synthetized using solid-phase peptide synthesis, and their minimal inhibitory concentration and haemolytic activity were tested. Furthermore, these two cruzioseptins plus three previously reported (CZS-1, CZS-2, CZS-3) were computationally characterized. Results show that cruzioseptins are 21-23 residues long alpha helical cationic peptides, with antimicrobial activity against E. coli, S. aureus, and C. albicans and low haemolytic effect. Docking results agree with the principal action mechanism of cationic AMPs that goes through cell membrane disruption due to electrostatic interactions between cationic residues in the cruzioseptins and negative phosphate groups in the pathogen cell membrane. An action mechanism through enzymes inhibition was also tried, but no conclusive results about this mechanism were obtained.

Silver nanoparticles as a potential treatment against SARS-CoV-2: A review.

Several human coronaviruses (HCoVs) are distinguished by the ability to generate epidemics or pandemics, with their corresponding diseases characterized by severe respiratory illness, such as that which occurs in severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and, today, in SARS-CoV-2, an outbreak that has struck explosively and uncontrollably beginning in December 2019 and has claimed the lives of more than 1.9 M people worldwide as of January 2021. The development of vaccines has taken one year, which is why it is necessary to investigate whether some already-existing alternatives that have been successfully developed in recent years can mitigate the pandemic's advance. Silver nanoparticles (AgNPs) have proved effective in antiviral action. Thus, in this review, several in vitro and in vivo studies of the effect of AgNPs on viruses that cause respiratory diseases are analyzed and discussed to promote an understanding of the possible interaction of AgNPs with SARS-CoV-2. The study focuses on several in vivo toxicological studies of AgNPs and a dose extrapolation to humans to determine the chief avenue of exposure. It can be concluded that the use of AgNPs as a possible treatment for SARS-CoV-2 could be viable, based on comparing the virus' behavior to that of similar viruses in in vivo studies, and that the suggested route of administration in terms of least degree of adverse effects is inhalation. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Synthesis of Silver Nanoparticles Using Aqueous Leaf Extract of Mimosa albida (Mimosoideae): Characterization and Antioxidant Activity.

The search for sensitive and rapid analytical techniques for the determination of natural antioxidants is an area in constant growth due, among other aspects, to the complexity of plant matrices. In this study, silver nanoparticles prepared with the aqueous extract of Mimosa albida leaves were used to assess their polyphenolic content and antioxidant capacity. Silver nanoparticles were characterized by different techniques. As a result, nanoparticles of 6.5 ± 3.1 nm were obtained. The total phenolic content in the extract was 1320.4 ± 17.6 mg of gallic acid equivalents GAE. 100 g-1 and in the nanoparticles 257.3 ± 5.1 mg GAE. 100 g-1. From the phenolic profile analyzed by ultra high-performance liquid chromatography (UPLC) with a diode-array detector (DAD), the presence of apigenin and luteolin in the plant extract is postulated. The antioxidant capacity measured by oxygen radical absorbance capacity ORAC-fluorescein assay was 86917 ± 6287 and 7563 ± 967 µmol ET g-1 in the extract and nanoparticles respectively. Electrochemical analysis by cyclic voltammetry (CV) confirmed the effective reduction capacity of the Mimosa albida leaves extract to reduce Ag ions to AgNPs and differential pulse voltammetry (DPV) suggested the presence of two main reducing agents in the extract. From this study, it was concluded that the aqueous extract of Mimosa albida contains reducing agents capable of synthesizing silver nanoparticles, which can be used in the phytochemical industry.

Green synthesis of silver nanoparticles using Solanum mammosum L. (Solanaceae) fruit extract and their larvicidal activity against Aedes aegypti L. (Diptera: Culicidae).

The family of mosquitoes (Diptera: Culicidae) contains several species of major public health relevance due to their role as vectors of human disease. One of these species, Aedes aegypti, is responsible for the transmission of some of the most important vector-borne viruses affecting humankind, including dengue fever, chikungunya and Zika. Traditionally, control of Ae. aegypti and other arthropod species has relied on the use of a relatively small diversity of chemical insecticides. However, widespread and intensive use of these substances has caused significant adverse environmental effects and has contributed to the appearance of pesticide-resistant populations in an increasing number of locations around the world, thereby dramatically reducing their efficiency. Therefore, it becomes urgent to develop novel alternative tools for vector control. In that context, our study aimed at evaluating the insecticidal activity against Ae. aegypti of aqueous extracts obtained from the fruits of Solanum mammosum L., as well as silver nanoparticles synthesized using aqueous extracts from this plant species (SmAgNPs). To perform the test, third instar Ae. aegypti larvae were exposed to increasing concentrations of plant extract and SmAgNPs for 24 h. Our results suggest that both the aqueous extract and SmAgNPs were toxic to the larvae, with SmAgNPs displaying a much higher level of toxicity than the extract alone, as reflected in their LC50 values (0.06 ppm vs 1631.27 ppm, respectively). These results suggest that both S. mammosum extracts and SmAgNPs exhibit noteworthy larvicidal activity, and should be further explored as potential source of alternative tools in the fight against insect vectors of human disease.

Molecular modeling of four Dermaseptin-related peptides of the gliding tree frog Agalychnis spurrelli.

In this research, we present a preliminary computational study of four Dermaseptin-related peptides from the skin exudate of the gliding tree frog Agalychnis spurrelli. Experimentally, the amino acid sequence of these peptides was elucidated through molecular cloning and tandem mass spectrometry and synthetic peptides were assayed against E. coli, S. aureus, and C. albicans to determine their antimicrobial properties. With the sequences on hand, a computational study of the structures was carried out, obtaining their physicochemical properties, secondary structure, and their similarity to other known peptides. A molecular docking study of these peptides was also performed against cell membrane and several enzymes are known to be vital for the organisms. Results showed that Dermaseptin-related peptides are α-helical cationic peptides with an isoelectric point above 9.70 and a positive charge of physiological pH. Introducing theses peptides in a database, it was determined that their identity compared with known peptides range from 36 to 82% meaning these four Dermaseptins are novel peptides. This preliminary study of molecular docking suggests the mechanism of action of this peptide is not given by the inhibition of essential enzymatic pathways, but by cell lysis. Graphical abstract.