Summary of the Current Status of DNA Vaccination for Alzheimer Disease.

Alzheimer disease (AD) is one of the most common and disabling neuropathies in the ever-growing aged population around the world, that especially affects Western countries. We are in urgent need of finding an effective therapy but also a valid prophylactic means of preventing AD. There is a growing attention currently paid to DNA vaccination, a technology particularly used during the COVID-19 era, which can be used also to potentially prevent or modify the course of neurological diseases, including AD. This paper aims to discuss the main features and hurdles encountered in the immunization and therapy against AD using DNA vaccine technology. Ultimately, this work aims to effectively promote the efforts in research for the development of safe and effective DNA and RNA vaccines for AD.

The inhibitory effects of platinum(II) complexes on amyloid aggregation: a theoretical and experimental approach.

Platinum (Pt)(II) square planar complexes are well-known anticancer drugs whose Mechanism of Action (MOA) are finely tuned by the polar, hydrophobic and aromatic features of the ligands. In the attempt to translate this tunability to the identification of potential neurodrugs, herein, four Pt(II) complexes were investigated in their ability to modulate the self-aggregation processes of two amyloidogenic models: Sup35p7-13 and NPM1264-277 peptides. In particular, phenanthriplatin revealed the most efficient agent in the modulation of amyloid aggregation: through several biophysical assays, as Thioflavin T (ThT), electrospray ionization mass spectrometry (ESI-MS) and ultraviolet-visible (UV-vis) absorption spectroscopy, this complex revealed able to markedly suppress aggregation and to disassemble small soluble aggregates. This effect was due to a direct coordination of phenanthriplatin to the amyloid, with the loss of several ligands and different stoichiometries, by the formation of π-π and π-cation interactions as indicated from molecular dynamic simulations. Presented data support a growing and recent approach concerning the repurposing of metallodrugs as potential novel neurotherapeutics.

Metal-Complexes Bearing Releasable CO Differently Modulate Amyloid Aggregation.

Neurodegenerative diseases are often associated with an uncontrolled amyloid aggregation. Hence, many studies are oriented to discover new compounds that are able to modulate self-recognition mechanisms of proteins involved in the development of these pathologies. Herein, three metal-complexes able to release carbon monoxide (CORMs) were analyzed for their ability to affect the self-aggregation of the amyloidogenic fragment of nucleophosmin 1, corresponding to the second helix of the three-helix bundle located in the C-terminal domain of the protein, i.e., NPM1264-277, peptide. These complexes were two cymantrenes coordinated to the nucleobase adenine (Cym-Ade) and to the antibiotic ciprofloxacin (Cym-Cipro) and a Re(I)-compound containing 1,10-phenanthroline and 3-CCCH2NHCOCH2CH2-6-bromo-chromone as ligands (Re-Flavo). Thioflavin T (ThT) assay, UV-vis absorption and fluorescence spectroscopies, scanning electron microscopy (SEM), and electrospray ionization mass spectrometry (ESI-MS) indicated that the three compounds have different effects on the peptide aggregation. Cym-Ade and Cym-Cipro act as aggregating agents. Cym-Ade induces the formation of NPM1264-277 fibers longer and stiffer than that formed by NPM1264-277 alone; irradiation of complexes speeds the formation of fibers that are more flexible and thicker than those found without irradiation. Cym-Cipro induces the formation of longer fibers, although slightly thinner in diameter. Conversely, Re-Flavo acts as an antiaggregating agent. Overall, these results indicate that metal-based CORMs with diverse structural features can have a different effect on the formation of amyloid fibers. A proper choice of ligands attached to metal can allow the development of metal-based drugs with potential application as antiamyloidogenic agents.

Hydrogelation tunability of bioinspired short peptides.

Supramolecular assemblies of short peptides are experiencing a stimulating flowering. Herein, we report a novel class of bioinspired pentapeptides, not bearing Phe, that form hydrogels with fibrillar structures. The inherent sequence comes from the fragment 269-273 of nucleophosmin 1 protein, that is normally involved in liquid-liquid phase separation processes into the nucleolus. By means of rheology, spectroscopy, and scanning microscopy the crucial roles of the extremities in the modulation of the mechanical properties of hydrogels were elucidated. Three of four peptide showed a typical shear-thinning profile and a self-assembly into hierarchical nanostructures fibers and two of them resulted biocompatible in MCF7 cells. The presence of an amide group at C-terminal extremity caused the fastest aggregation and the major content of structured intermediates during gelling process. The tunable mechanical and structural features of this class of hydrogels render derived supramolecular systems versatile and suitable for future biomedical applications.

Small molecules enhancers of amyloid aggregation of C-terminal domain of Nucleophosmin 1 in acute myeloid leukemia.

The "Acute Myeloid Leukemia with gene mutations'' group includes mutations in Nucleophosmin 1(NPM1) that is an abundant multifunctional protein with chaperon functions. This protein also takes part to rRNA maturation in ribosome biogenesis, tumor suppression and nucleolar stress response. Mutations of NPM1 associated to AML present in its C-terminal domain (CTD) unable its correct folding and confer it an aberrant cytoplasmatic localization (NPMc+). AML cells with NPM1 mutations retain a certain amount of wt NPM1 in the nucleolus and since NPM1 acts as a hub protein, the nucleolus of AML cells are more vulnerable with respect to cells expressing only wt NPM1. Thus, interfering with the levels or the oligomerization status of NPM1 may influence its capability to properly build up the nucleolus in AML cells. Our biophysical recent results demonstrated that AML-CTDs contain regions prone to amyloid aggregation and, herein, we present results oriented to exploit this amylodogenesis in a potential therapeutic way. We evaluated the different ability of two small molecules to enhance amyloid aggregation through complementary biophysical approaches as fluorescence and Circular Dichroism spectroscopies, Scanning Electron Microscopy and cell-viability assays, to evaluate the cytoxicity of these molecules in AML cells lines. These findings could pave the way into molecular mechanisms of NPM1c and in novel therapeutic routes toward AML progression.

The Healing Power of Clean Rivers: In Silico Evaluation of the Antipsoriatic Potential of Apiin and Hyperoside Plant Metabolites Contained in River Waters.

Humanity may benefit greatly from intact riverine ecosystems not only because they supply water to be used in the most common human activities, but also for the effects that clean rivers can have on human health. Herein, we used a computational approach to show that some phytochemicals produced by riparian plants as secondary metabolites, which are naturally released into river waters, can have therapeutic properties. These include antipsoriatic activities which we demonstrated in silico by modelling the interaction of apiin, guanosine and hyperoside, a few main river plant metabolites, with NF-kB, IL-17 and IL-36, which are recognized targets involved in psoriasis disease. In particular, we found that apiin and hyperoside are endowed with docking energies and binding affinities which are more favorable than the known reference inhibitors of the three protein targets whilst, in silico, guanosine shows comparable activity with respect to the inhibitors of IL-36 and NF-kB. The low skin permeation (logKp < −8) we predicted for apiin and hyperoside led us to hypothesize their possible utilization as topic antipsoriatic therapeutics, and in particular after PAINS (pan-assay interference compounds) score evaluation, we reached the conclusion that apiin, with no predicted tendency to react nonspecifically with the numerous targets involved in the biological cellular pathways, is particularly interesting for the desired therapeutic application.

Old growth forests and large old trees as critical organisms connecting ecosystems and human health. A review.

Old forests containing ancient trees are essential ecosystems for life on earth. Mechanisms that happen both deep in the root systems and in the highest canopies ensure the viability of our planet. Old forests fix large quantities of atmospheric CO2, produce oxygen, create micro-climates and irreplaceable habitats, in sharp contrast to young forests and monoculture forests. The current intense logging activities induce rapid, adverse effects on our ecosystems and climate. Here we review large old trees with a focus on ecosystem preservation, climate issues, and therapeutic potential. We found that old forests continue to sequester carbon and fix nitrogen. Old trees control below-ground conditions that are essential for tree regeneration. Old forests create micro-climates that slow global warming and are irreplaceable habitats for many endangered species. Old trees produce phytochemicals with many biomedical properties. Old trees also host particular fungi with untapped medicinal potential, including the Agarikon, Fomitopsis officinalis, which is currently being tested against the coronavirus disease 2019 (COVID-19). Large old trees are an important part of our combined cultural heritage, providing people with aesthetic, symbolic, religious, and historical cues. Bringing their numerous environmental, oceanic, ecological, therapeutic, and socio-cultural benefits to the fore, and learning to appreciate old trees in a holistic manner could contribute to halting the worldwide decline of old-growth forests.

Less COVID-19 deaths in southern and insular Italy explained by forest bathing, Mediterranean environment, and antiviral plant volatile organic compounds.

The coronavirus disease 2019 (COVID-19) is causing major sanitary and socioeconomic issues, yet some locations are less impacted than others. While densely populated areas are likely to favor viral transmission, we hypothesize that other environmental factors could explain lower cases in some areas. We studied COVID-19 impact and population statistics in highly forested Mediterranean Italian regions versus some northern regions where the amount of trees per capita is much lower. We also evaluated the affinity of Mediterranean plant-emitted volatile organic compounds (VOCs) isoprene, α-pinene, linalool and limonene for COVID-19 protein targets by molecular docking modeling. Results show that while mean death number increased about 4 times from 2020 to 2021, the percentage of deaths per population (0.06-0.10%) was lower in the greener Mediterranean regions such as Sardinia, Calabria and Basilica versus northern regions with low forest coverage, such as Lombardy (0.33%) and Emilia Romagna (0.29%). Data also show that the pandemic severity cannot be explained solely by population density. Modeling reveals that plant organic compounds could bind and interfere with the complex formed by the receptor binding domain of the coronavirus spike protein with the human cell receptor. Overall, our findings are likely explained by sea proximity and mild climate, Mediterranean diet and the abundance of non-deciduous Mediterranean plants which emit immunomodulatory and antiviral compounds. Potential implications include 'forest bathing' as a therapeutic practice, designing nasal sprays containing plant volatile organic compounds, and preserving and increasing forest coverage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10311-021-01309-5.

Forest-bathing and physical activity as weapons against COVID-19: a review.

Strengthening the immune system in order to better withstand the threat of COVID-19 is an important way to ensure the protection of our health against the current pandemic associated with SARS-CoV-2. There are many ways to achieve this, but with current circumstances, certain modalities stand out as being the most valid and are certainly worth greater consideration. Here we review the effects that particular immuno-strengthening activities can have on limiting the severity of COVID-19 disease as well as preventing virus infection. Physical activity, in particular, should not be discounted as an important method of prevention of viral diseases as it triggers many biological processes within the human body which in turn lead to heightened natural defences against viral infections. When exercise is performed in forested areas, these protective health benefits may be increased since many plant species emit biogenic volatile compounds (VOCs) which, when inhaled, have many protective properties. These VOCs have been shown in particular to have immunostimulatory effects on the human body and, thus, they could be of use in the prevention and/or treatment of COVID-19. Being amongst trees may also help to alleviate stress and anxiety, lowering cortisol levels and consequently helping the proper functioning of the immune system. In the following work, we have performed an analysis of the available scientific literature which looks at the effects of physical exercise as well as 'forest-bathing' on the immune system's ability to fight disease, especially of course as it relates to COVID-19. Our review aims at shedding light on the benefits of exercising outdoors in green areas and suggests reforestation as a protective measure against future outbreaks.

Assessment of Copper and Heavy Metals in Family-Run Vineyard Soils and Wines of Campania Region, South Italy.

Copper-based phytosanitary treatments are widely employed in viticulture for combating the fungal diseases of European grape (Vitis vinifera L.). Herein we evaluated copper accumulation in the soil of a 50-year-old still productive vineyard in South Italy in comparison with samples taken from a 'control' area in which grapevines had never been cultivated, as well from an abandoned vineyard, now planted with cereals and forage crops, both close to the main area under investigation. Even though the heavy metal contents detected were not of concern for soils nor for wine, Cu accumulates in the soil in amounts significantly higher than the (grapevine free) control and remains at detectable concentrations also in abandoned vineyards where spraying activities had ceased about 20 years before this study. Despite the long Cu residence times in soil, the wine produced with grapes of the same vineyard showed Cu levels low enough to be safely used for human consumption, probably due to mechanisms of metal precipitation occurring during wine maturation, which are typically accompanied by sedimentation processes in artisanal production. However, this should not diminish the urgency of decreasing the copper usage as antifungal remedy in viticulture to prevent copper contamination of the agricultural soils.

Molecular Basis of the Therapeutical Potential of Clove (Syzygium aromaticum L.) and Clues to Its Anti-COVID-19 Utility.

The current COronaVIrus Disease 19 (COVID-19) pandemic caused by SARS-CoV-2 infection is enormously affecting the worldwide health and economy. In the wait for an effective global immunization, the development of a specific therapeutic protocol to treat COVID-19 patients is clearly necessary as a short-term solution of the problem. Drug repurposing and herbal medicine represent two of the most explored strategies for an anti-COVID-19 drug discovery. Clove (Syzygium aromaticum L.) is a well-known culinary spice that has been used for centuries in folk medicine in many disorders. Interestingly, traditional medicines have used clove since ancient times to treat respiratory ailments, whilst clove ingredients show antiviral and anti-inflammatory properties. Other interesting features are the clove antithrombotic, immunostimulatory, and antibacterial effects. Thus, in this review, we discuss the potential role of clove in the frame of anti-COVID-19 therapy, focusing on the antiviral, anti-inflammatory, and antithrombotic effects of clove and its molecular constituents described in the scientific literature.

Supramolecular aggregation of colloidal natural organic matter masks priority pollutants released in water from peat soil.

Natural organic matter (NOM) from Sphagnum peat soil is extracted in water and subjected to several investigations to obtain structural and conformational information. Data show that the extracted NOM is self-organized in colloidal aggregates of variable sizes (from nano to micro scales, depending on the solvent composition, i.e., ultrapure water, solutions with denaturing agents, acetone, ethanol). Aggregates are formed by highly heterogeneous classes of organic compounds. According to the results of nuclear magnetic resonance and fluorescence measurements, the three-dimensional structure of aggregates, revealed by scanning electron microscope imaging, is supposed to be stabilized by the exposition of polar functional groups to the solvent, with consequent formation of hydrogen bonds, dipole-interactions and cation bridging. In contrast, the inner part of the aggregates displays hydrophobic features and is hypothesized to be further reinforced by the establishment of π-stacking interactions. The structure is assumed to be a supramolecular aggregation of small-medium oligomeric fragments (Max 750 Da) in which priority pollutants are entrapped by dispersive forces. The structures are shown to be nanosized spheroidal particles further aggregated to form higher dimension supra-structures. Carbohydrates play primary role, stabilizing the structure and giving marked hydrophilic properties to the aggregates.

Evidence of Protein Binding by a Nucleopeptide Based on a Thyminedecorated L-Diaminopropanoic Acid through CD and In Silico Studies.

BACKGROUND: Nucleopeptides are chimeric compounds of biomedical importance carrying DNA nucleobases anchored to peptide backbones with the ascertained capacity to bind nucleic acids. However, their ability to interact with proteins involved in pathologies of social relevance is a feature that still requires investigation. The worrying situation currently observed worldwide for the COVID-19 pandemic urgently requires the research on novel anti-SARSCoV- 2 molecular weapons, whose discovery can be aided by in silico predictive studies. OBJECTIVE: The aim of this work is to explore by spectroscopic methods novel features of a thymine-bearing nucleopeptide based on L-diaminopropanoic acid, including conformational aspects as well as its ability to bind proteins, starting from bovine serum albumin (BSA) as a model protein. Moreover, in consideration of the importance of targeting viral proteins in the current fight against COVID-19, we evaluated in silico the interaction of the nucleopeptide with some of the most relevant coronavirus protein targets. METHODS: First, we investigated via circular dichroism (CD) the conformational behaviour of this thymine-bearing nucleopeptide with temperature: we observed CD spectral changes, particularly passing from 15 to 35 °C. Scanning Electron Microscopy (SEM) analysis of the nucleopeptide was also conducted on nucleopeptide solid samples. Additionally, CD binding and preliminary in silico investigations were performed with BSA as a model protein. Moreover, molecular dockings were run using as targets some of the main SARS-CoV-2 proteins. RESULTS: The temperature-dependent CD behaviour reflected the three-dimensional rearrangement of the nucleopeptide at different temperatures, with higher exposure to the solvent of its chromophores at higher temperatures compared to a more stacked structure at a low temperature. SEM analysis of nucleopeptide samples in the solid-state showed a granular morphology, with a low roughness and some thread structures. Moreover, we found through spectroscopic studies that the modified peptide bound the albumin target by inducing significant changes to the protein secondary structure. CONCLUSION: CD and preliminary in silico studies suggested that the nucleopeptide bound the BSA protein with high affinity according to different binding modes, as testified by binding energy scores lower than -11 kcal/mol. Interestingly, a predictive study performed on 3CLpro and other SARS-CoV-2 protein targets suggested the potential ability of the nucleopeptide to bind with good affinity the main protease of the virus and other relevant targets, including the RNAdependent RNA polymerase, especially when complexed with RNA, the papain-like protease, and the coronavirus helicase at the nucleic acid binding site.

Fabrication of fluorescent nanospheres by heating PEGylated tetratyrosine nanofibers.

Aromatic polypeptides have recently drawn the interest of the research community for their capability to self-assemble into a variety of functional nanostructures. Due to their interesting mechanical, electrical and optical properties, these nanostructures have been proposed as innovative materials in different biomedical, biotechnological and industrial fields. Recently, several efforts have been employed in the development of these innovative materials as nanoscale fluorescence (FL) imaging probes. In this context, we describe the synthesis and the functional properties of a novel fluorescent tyrosine (Tyr, Y)-based nanospheres, obtained by heating at 200 °C a solution of the PEGylated tetra-peptide PEG6-Y4. At room temperature, this peptide self-assembles into not fluorescent low ordered water-soluble fibrillary aggregates. After heating, the aggregation of different polyphenolic species generates Y4-based nanospheres able to emit FL into blue, green and red spectral regions, both in solution and at the solid state. The aggregation features of PEG6-Y4 before and after heating were studied using a set of complementary techniques (Fluorescence, CD, FT-IR, Small and Wide-Angle X-ray Scattering and SEM). After a deep investigation of their optoelectronic properties, these nanospheres could be exploited as promising tools for precise biomedicine in advanced nanomedical technologies (local bioimaging, light diagnostics, therapy, optogenetics and health monitoring).

Lower COVID-19 mortality in Italian forested areas suggests immunoprotection by Mediterranean plants.

The COVID-19 pandemic has induced dramatic effects on the population of the industrialized north of Italy, whereas it has not heavily affected inhabitants of the southern regions. This might be explained in part by human exposure to high levels of fine particulate matter (PM) in the air of northern Italy, thus exacerbating the mortality. Since trees mitigate air pollution by intercepting PM onto plant surfaces and bolster the human immune system by emitting bioactive volatile organic compounds (VOCs), we hypothesize a protective role of evergreen forested areas in southern Italy. We compared the mortality rate  due to COVID-19, the death number, the positivity rate and the forest coverage per capita in various Italian regions. Hectares of forest per capita and prevalence of deciduous versus evergreen forestal species were also estimated. In silico docking studies of potentially protective compounds found in Laurus nobilis L., a typical Mediterranean plant, were performed to search for potential antivirals. We found that the pandemic's severity was generally lower in southern regions, especially those with more than 0.3 hectares of forest per capita. The lowest mortality rates were found in southern Italy, mainly in regions like Molise (0.007%) and Basilicata (0.005%) where the forest per capita ratio is higher than 0.5 Ha/person. Our findings suggest that evergreen Mediterranean forests and shrubland plants could have protected the southern population by emission of immuno-modulating VOCs and provision of dietary sources of bioactive compounds. Moreover, in silico studies revealed a potential anti-COVID-19 activity in laurusides, which are unexplored glycosides from bay laurel. Overall, our results highlight the importance of nature conservation and applications to the search for natural antivirals.

Evaluating In Silico the Potential Health and Environmental Benefits of Houseplant Volatile Organic Compounds for an Emerging 'Indoor Forest Bathing' Approach.

The practice of spending time in green areas to gain the health benefits provided by trees is well known, especially in Asia, as 'forest bathing', and the consequent protective and experimentally detectable effects on the human body have been linked to the biogenic volatile organic compounds released by plants. Houseplants are common in houses over the globe and are particularly appreciated for aesthetic reasons as well for their ability to purify air from some environmental volatile pollutants indoors. However, to the best of our knowledge, no attempt has been made to describe the health benefits achievable from houseplants thanks to the biogenic volatile organic compounds released, especially during the day, from some of them. Therefore, we performed the present study, based on both a literature analysis and in silico studies, to investigate whether the volatile compounds and aerosol constituents emitted by some of the most common houseplants (such as peace lily plant, Spathiphyllum wallisii, and iron plant, Aspidistra eliator) could be exploited in 'indoor forest bathing' approaches, as proposed here for the first time not only in private houses but also public spaces, such as offices, hospitals, and schools. By using molecular docking (MD) and other in silico methodologies for estimating vapor pressures and chemico-physical/pharmacokinetic properties prediction, we found that ß-costol is an organic compound, emitted in appreciable amounts by the houseplant Spathiphyllum wallisii, endowed with potential antiviral properties as emerged by our MD calculations in a SARS-CoV-2 Mpro (main protease) inhibition study, together with sesquirosefuran. Our studies suggest that the anti-COVID-19 potential of these houseplant-emitted compounds is comparable or even higher than known Mpro inhibitors, such as eugenol, and sustain the utility of houseplants as indoor biogenic volatile organic compound emitters for immunity boosting and health protection.

Distribution and Characterization of Deep Rhodolith Beds off the Campania coast (SW Italy, Mediterranean Sea).

Rhodolith beds (RBs) are bioconstructions characterized by coralline algae, which provide habitat for several associated species. Mediterranean RBs are usually located in the mesophotic zone (below 40 m), and thus are frequently remote and unexplored. Recently, the importance and vulnerability of these habitats have been recognized by the European Community and more attention has been drawn to their investigation and conservation. This study reports the results of an extensive monitoring program, carried out within the Marine Strategy Framework Directive (2008/56/EC), in six sites off the Campania coast (Italy, Mediterranean Sea). New insights were given into the distribution, cover, vitality (i.e., live/dead rhodolith ratio), structural complexity, and coralline algae composition of RBs. Remotely operated vehicles (ROV) investigations allowed the description of several RBs, and the discovery of a RB with rhodolith cover >65% offshore the Capri Island. Only two sites (Secchitiello and Punta Campanella) showed a very low mean cover of live rhodoliths (<10%); hence, not being classifiable as RBs. The collected rhodoliths were mostly small pralines (~2 cm), spheroidal to ellipsoidal, with growth-forms ranging from encrusting/warty to fruticose/lumpy. Coralline algae identification revealed a high diversity within each bed, with a total of 13 identified taxa. The genus Lithothamnion dominated all sites, and Phymatolithon calcareum and Lithothamnion corallioides, protected by the Habitats Directive (92/43/EEC), were detected in all RBs.

Biological macromolecule binding and anticancer activity of synthetic alkyne-containing L-phenylalanine derivatives.

Herein, we described the synthesis of two L-phenylalanines α-derivatized with a terminal alkyne moiety whose structures differed by phenyl ring halogen substitution (two o-Cl in 1 vs. one p-Br in 2) and investigated their effect on biological macromolecules and living cells. We explored their interaction with quadruplex DNA (G4 DNA), using tel26 and c-myc as models, and bovine serum albumin (BSA). By CD spectroscopy, we found that 1 caused minor tel26 secondary structure changes, leading also to a slight thermal stabilization of this hybrid antiparallel/parallel G4 structure, while the c-myc parallel topology remained essentially unchanged upon 1 binding. Other CD evidences showed the ability of 1 to bind BSA, while molecular docking studies suggested that the same molecule could be housed into the hydrophobic cavity between sub-domains IIA, IIB, and IIIA of the protein. Furthermore, preliminary aggregation studies, based on concentration-dependent spectroscopic experiments, suggested the ability of 1 to aggregate forming noncovalent polymeric systems in aqueous solution. Differently from 1, the bromine-modified compound was able to bind Cu(II) ion, likely with the formation of a CuL2 complex, as found by UV spectroscopy. Finally, cell tests excluded any cytotoxic effect of both compounds toward normal cells, but showed slight antiproliferative effects of 2 on PC3 cancerous cells at 24 h, and of 1 on both T98G and MDA-MB-231 cancer cells at 48 h.

A New Strategy to Produce Hemp Fibers through a Waterglass-Based Ecofriendly Process.

Natural fibers such as kenaf, hemp, flax, jute, and sisal have become the subject of much research as potential green or eco-friendly reinforcement composites, since they assure the reduction of weight, cost, and CO2 release with less reliance on oil sources. Herein, an inexpensive and eco-friendly waterglass treatment is proposed, allowing the production of silica-coated fibers that can be easily obtained in micro/nano fibrils through a low power mixer. The silica coating has been exploited to improve the chemical compatibility between fibers and the polymer matrix through the reaction of silanol groups with suitable coupling agents. In particular, silica-coated fibers easily functionalized with (3-Aminopropyl) triethoxysilane (APTS) were used as a filler in the manufacturing of epoxy-based composites. Morphological investigation of the composites through Scanning Electron Microscopy (SEM) demonstrated that the filler has a tendency to produce a web-like structure, formed by continuously interconnected fibrils and microfibrils, from which particularly effective mechanical properties may be obtained. Dynamic Mechanical Analysis (DMA) shows that the functionalized fibers, in a concentration of 5 wt%, strongly affect the glass transformation temperature (10 °C increase) and the storage modulus of the pristine resin. Taking into account the large number of organosilicon compounds (in particular the alkoxide ones) available on the market, the new process appears to pave the way for the cleaner and cheaper production of biocomposites with different polymeric matrices and well-tailored interfaces.