Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products: potential pH-dependent inhibition explored through computer-aided drug design.

Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite's N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite's changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.

Green Synthesis of Silver Nanoparticles Mediated by Punica granatum Peel Waste: An Effective Additive for Natural Rubber Latex Nanofibers Enhancement.

Pomegranate waste poses an environmental challenge in Arequipa. Simultaneously, interest in sustainable materials like natural rubber latex (NRL) is growing, with Peruvian communities offering a promising source. This study explores the green synthesis of silver nanoparticles (AgNPs) using pomegranate peel extract and their incorporation into NRL nanofibers for enhanced functionalities. An eco-friendly process utilized silver nitrate and pomegranate peel extract as a reducing and capping agent to synthesize AgNPs. The resulting AgNPs and NRL/AgNPs nanofibers were characterized using imaging and spectroscopic techniques such as UV-vis, TGA, FTIR, XRD, Raman, SEM, and DLS. Green-synthesized AgNPs were spherical and crystalline, with an average diameter of 59 nm. They showed activity against K. pneumoniae, E. coli, B. cereus, and S. aureus (IC50: 51.32, 4.87, 27.72, and 69.72 µg/mL, respectively). NRL and NRL/AgNPs nanofibers (300-373 nm diameter) were successfully fabricated. The composite nanofibers exhibited antibacterial activity against K. pneumoniae and B. cereus. This study presents a sustainable approach by utilizing pomegranate waste for AgNP synthesis and NRL sourced from Peruvian communities. Integrating AgNPs into NRL nanofibers produced composites with antimicrobial properties. This work has potential applications in smart textiles, biomedical textiles, and filtration materials where sustainability and antimicrobial functionality are crucial.

Computer-aided drug design approaches applied to screen natural product's structural analogs targeting arginase in Leishmania spp.

Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics-generalized Born surface area (MM-GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions by MM-GBSA and FEP methods. Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated.

The Potential of Xylooligosaccharides as Prebiotics and Their Sustainable Production from Agro-Industrial by-Products.

In recent years, concerns about a good-quality diet have increased. Food supplements such as prebiotics have great nutritional and health benefits. Within the diverse range of prebiotics, xylooligosaccharides (XOs) show high potential, presenting exceptional properties for the prevention of systemic disorders. XOs can be found in different natural sources; however, their production is limited. Lignocellulosic biomasses present a high potential as a source of raw material for the production of XOs, making the agro-industrial by-products the perfect candidates for production on an industrial scale. However, these biomasses require the application of physicochemical pretreatments to obtain XOs. Different pretreatment methodologies are discussed in terms of increasing the production of XOs and limiting the coproduction of toxic compounds. The advance in new technologies for XOs production could decrease their real cost (USD 25-50/kg) on an industrial scale and would increase the volume of market transactions in the prebiotic sector (USD 4.5 billion). In this sense, new patents and innovations are being strategically developed to expand the use of XOs as daily prebiotics.

Biogenic Synthesis of Copper Nanoparticles: A Systematic Review of Their Features and Main Applications.

Nanotechnology is an innovative field of study that has made significant progress due to its potential versatility and wide range of applications, precisely because of the development of metal nanoparticles such as copper. Nanoparticles are bodies composed of a nanometric cluster of atoms (1-100 nm). Biogenic alternatives have replaced their chemical synthesis due to their environmental friendliness, dependability, sustainability, and low energy demand. This ecofriendly option has medical, pharmaceutical, food, and agricultural applications. When compared to their chemical counterparts, using biological agents, such as micro-organisms and plant extracts, as reducing and stabilizing agents has shown viability and acceptance. Therefore, it is a feasible alternative for rapid synthesis and scaling-up processes. Several research articles on the biogenic synthesis of copper nanoparticles have been published over the past decade. Still, none provided an organized, comprehensive overview of their properties and potential applications. Thus, this systematic review aims to assess research articles published over the past decade regarding the antioxidant, antitumor, antimicrobial, dye removal, and catalytic activities of biogenically synthesized copper nanoparticles using the scientific methodology of big data analytics. Plant extract and micro-organisms (bacteria and fungi) are addressed as biological agents. We intend to assist the scientific community in comprehending and locating helpful information for future research or application development.

A Systematic Review and Meta-Analysis Comparing the Diagnostic Accuracy Tests of COVID-19.

In this paper, we present a systematic review and meta-analysis that aims to evaluate the reliability of coronavirus disease diagnostic tests in 2019 (COVID-19). This article seeks to describe the scientific discoveries made because of diagnostic tests conducted in recent years during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Between 2020 and 2021, searches for published papers on the COVID-19 diagnostic were made in the PubMed database. Ninety-nine scientific articles that satisfied the requirements were analyzed and included in the meta-analysis, and the specificity and sensitivity of the diagnostic accuracy were assessed. When compared to serological tests such as the enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CLIA), lateral flow immunoassay (LFIA), and chemiluminescent microparticle immunoassay (CMIA), molecular tests such as reverse transcription polymerase chain reaction (RT-PCR), reverse transcription loop-mediated isothermal amplification (RT-LAMP), and clustered regularly interspaced short palindromic repeats (CRISPR) performed better in terms of sensitivity and specificity. Additionally, the area under the curve restricted to the false-positive rates (AUCFPR) of 0.984 obtained by the antiviral neutralization bioassay (ANB) diagnostic test revealed significant potential for the identification of COVID-19. It has been established that the various diagnostic tests have been effectively adapted for the detection of SARS-CoV-2; nevertheless, their performance still must be enhanced to contain potential COVID-19 outbreaks, which will also help contain potential infectious agent outbreaks in the future.

Alzheimer's Disease: A Silent Pandemic - A Systematic Review on the Situation and Patent Landscape of the Diagnosis.

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive impairment, tau protein deposits, and amyloid beta plaques. AD impacted 44 million people in 2016, and it is estimated to affect 100 million people by 2050. AD is disregarded as a pandemic compared with other diseases. To date, there is no effective treatment or diagnosis. OBJECTIVE: We aimed to discuss the current tools used to diagnose COVID-19, point out their potential to be adapted for AD diagnosis, and review the landscape of existing patents in the AD field and future perspectives for AD diagnosis. METHODS: We carried out a scientific screening following a research strategy in PubMed; Web of Science; the Derwent Innovation Index; the KCI-Korean Journal Database; Sci- ELO; the Russian Science Citation index; and the CDerwent, EDerwent, and MDerwent index databases. RESULTS: A total of 326 from 6,446 articles about AD and 376 from 4,595 articles about COVID-19 were analyzed. Of these, AD patents were focused on biomarkers and neuroimaging with no accurate, validated diagnostic methods, and only 7% of kit development patents were found. In comparison, COVID-19 patents were 60% about kit development for diagnosis; they are highly accurate and are now commercialized. CONCLUSION: AD is still neglected and not recognized as a pandemic that affects the people and economies of all nations. There is a gap in the development of AD diagnostic tools that could be filled if the interest and effort that has been invested in tackling the COVID-19 emergency could also be applied for innovation.

In Silico Analysis of Metabolites from Peruvian Native Plants as Potential Therapeutics against Alzheimer's Disease.

BACKGROUND: Despite research on the molecular bases of Alzheimer's disease (AD), effective therapies against its progression are still needed. Recent studies have shown direct links between AD progression and neurovascular dysfunction, highlighting it as a potential target for new therapeutics development. In this work, we screened and evaluated the inhibitory effect of natural compounds from native Peruvian plants against tau protein, amyloid beta, and angiotensin II type 1 receptor (AT1R) pathologic AD markers. METHODS: We applied in silico analysis, such as virtual screening, molecular docking, molecular dynamics simulation (MD), and MM/GBSA estimation, to identify metabolites from Peruvian plants with inhibitory properties, and compared them to nicotinamide, telmisartan, and grapeseed extract drugs in clinical trials. RESULTS: Our results demonstrated the increased bioactivity of three plants' metabolites against tau protein, amyloid beta, and AT1R. The MD simulations indicated the stability of the AT1R:floribundic acid, amyloid beta:rutin, and tau:brassicasterol systems. A polypharmaceutical potential was observed for rutin due to its high affinity to AT1R, amyloid beta, and tau. The metabolite floribundic acid showed bioactivity against the AT1R and tau, and the metabolite brassicasterol showed bioactivity against the amyloid beta and tau. CONCLUSIONS: This study has identified molecules from native Peruvian plants that have the potential to bind three pathologic markers of AD.

Antiviral Activity of Metabolites from Peruvian Plants against SARS-CoV-2: An In Silico Approach.

(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. (2) Methods: We applied in silico technics, such as virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA estimation. (3) Results: Rutin, a compound present in Peruvian native plants, showed affinity against three targets of SARS-CoV-2. The molecular dynamics simulation demonstrated the high stability of receptor-ligand systems during the time of the simulation. Our results showed that the Mpro-Rutin system exhibited higher binding free energy than PLpro-Rutin and N-Rutin systems through MM/GBSA analysis. (4) Conclusions: Our study provides insight on natural metabolites from Peruvian plants with therapeutical potential. We found Rutin as a potential candidate with multiple pharmacological properties against SARS-CoV-2.

In vitro cytotoxic effect of a chitin-like polysaccharide produced by Mortierella alpina on adrenocortical carcinoma cells H295R, and its use as mitotane adjuvant.

This study presents an in vitro evaluation of the antitumor potential of a chitin-like exopolysaccharide (EPS, produced by Mortierella alpina) on Adrenocortical carcinoma cells (ACC) compared to mitotane, a commercial drug commonly used in ACC treatment, and known for its side effects. Techniques of cellular viability determination such as MTT and fluorescence were used to measure the cytotoxic effects of the EPS and mitotane in tumoral cells (H295R) and non-tumoral cells (VERO), observing high cytotoxicity of mitotane and a 10% superior pro-apoptotic effect of the EPS compared to mitotane (p < 0.05). The cytotoxic effect of the EPS was similar to the effect of 50 µM mitotane on tumoral cells (p < 0.05). A decrement of the lysosomal volume was also noted in tumoral cells treated with the EPS. To enhance the antitumor effect, a combination of mitotane at a lower dosage and the EPS (as adjuvant) was also tested, showing a slight improvement of the cytotoxicity effect on tumoral cells. Therefore, the results indicate a cytotoxic effect of the EPS produced by Mortierella alpina on adrenocortical carcinoma, and a possible application in biomedical formulations or additional treatments.