Product Database Research Articles

Latin American Natural Product Database (LANaPDB): An Update.

Natural product (NP) databases are crucial tools in computer-aided drug design (CADD). Over the past decade, there has been a worldwide effort to assemble information regarding natural products (NPs) isolated and characterized in certain geographical regions. In 2023, it was published LANaPDB, and to our knowledge, this is the first attempt to gather and standardize all the NP databases of Latin America. Herein, we present and analyze in detail the contents of an updated version of LANaPDB, which includes 619 newly added compounds from Colombia, Costa Rica, and Mexico. The present version of LANaPDB has a total of 13 578 compounds, coming from ten databases of seven Latin American countries. A chemoinformatic characterization of LANaPDB was carried out, which includes the structural classification of the compounds, calculation of six physicochemical properties of pharmaceutical interest, and visualization of the chemical space by employing and comparing two different fingerprints (MACCS keys (166-bit) and Morgan2 (2048-bit)). Furthermore, additional analyses were made, and valuable information not included in the first version of LANaPDB was added, which includes structural diversity, molecular complexity, synthetic feasibility, commercial availability, and reported and predicted biological activity. In addition, the LANaPDB compounds were cross-referenced to two of the largest public chemical compound databases annotated with biological activity: ChEMBL and PubChem.

Vibrational, theoretical characterisation and In Silico investigation of Norcinnamolaurine: a natural lead for inhibiting AURKA and overcoming immune evasion in Triple-Negative Breast Cancer

ABSTRACT Alkaloids represent a diverse category of natural compounds with noteworthy pharmacological and therapeutic applications. Benzylisoquinoline alkaloids (BIAs) are distinguished by their varied structures and potential medicinal properties. This study specifically investigates Norcinnamolaurine, a BIA found in multiple species and acknowledged for its therapeutic advantages. In the current investigation, we comprehensively analyzed Norcinnamolaurine, encompassing Frontier Molecular Orbital studies, vibrational spectroscopy, nonlinear optical properties, natural bond orbital evaluations, and Fukui's analysis. Additionally, we executed an E-pharmacophore-based screening utilizing the AURKA-Norcinnamolaurine complex. The generated hypothesis underwent database screening; lead compounds from the Natural Product and Drug Bank databases exhibited enhanced binding affinities ranging from −8.602 to −7.148 kcal/mol, demonstrating improved interactions within the AURKA binding pocket. Subsequently, the identified lead compounds were subjected to further analysis via MMGBSA, DFT, and Molecular Dynamics Simulations (MDS). Our findings indicate that Norcinnamolaurine exhibits a superior binding affinity towards the target protein. Significant outcomes were also observed in the vibrational and FMO studies. Moreover, MDS analysis revealed that the resultant complexes maintained relative stability, exhibiting minimal deviation and fluctuations. This stability was corroborated through additional assessments using MMPBSA and PCA/FEL methodologies.

Identification of Phytoconstituents from Natural Product Database as SIRT2 Inhibitors for Potential Role in Alzheimer's Disease: An In-Silico Screening.

We aimed to conduct in silico screening of the potential phytoconstituent from a natural product database to find SIRT2 inhibitors. Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by behavioral and mental symptoms as well as a progressive loss of cognitive ability. Since SIRT2 may be detrimental to neurological illnesses, it is a prime target for research into SIRT2 inhibitors. To identify the SIRT2 inhibitors and their role in AD. We have utilized NPAtlas database and screened using pharmacophore-based virtual screening, molecular docking, and simulation. The Natural Products Atlas provides unrestricted access to various natural products derived from bacteria and fungi, allowing researchers to investigate and visualize the extensive chemical diversity in the natural world. From in silico screening data, we have found phytoconstituents that could function as SIRT2 inhibitors. Six phytoconstituents were identified using pharmacophore-based virtual screening. According to molecular docking, Kurasoin B outperformed the reference molecule regarding binding energy. Kurasoin B exhibited a binding affinity of -12.543 kcal/mol, whereas the binding affinity of the reference molecule was -12.089 kcal/mol. The Kurasoin B complex with SIRT2 was determined to be stable throughout the simulation by performing MD simulation, with an RMSD of 2.88 (Å), whereas the reference and free protein displayed RMSDs of 3.74 and 4.70 (Å), respectively. In silico studies and data analysis, suggest that Kurasoin B may be able to suppress the SIRT2 protein for managing AD.

Identification of Potential Inhibitors of TGFβR1 for the treatment of Cancer through Structure-based virtual screening and Molecular dynamics simulations.

Globally, cancer is one of the leading causes of death. Resistance to conventional medications, such as chemotherapy and radiation, continues to be a significantchallenge in the treatment of cancerdespite the availability of numerous medicines. Therefore, the highest priority is to hunt for new therapeutic agents. Transforming growth factor-beta is a pivotal regulatory cytokine that exerts significant influence over cellular processes, particularly emphasizing its role in facilitating and modulating cell proliferation. TGFβ1,identified asmost promising active site of the TGF-β signaling, is a potent drug target site that has garnered wide attention for developing new anticancer agents. The present investigation investigates the potential phytochemicals as TGFβR1 inhibitors. The SB431542 complexed TGFβR1 protein model was used to screen the natural product database to obtain a compound with high binding potential. NPC247629 has emerged as the best-scored compound among all the screened compounds, demonstrating the highest affinity towards the TGFβR1 regarding docking score -17.54 kcal/mol. TheMD simulation study indicated that all proposed hits are retained inside the receptor in dynamic states. The best-screened hits, NPC247629 and NPC60735, have excellent binding affinity and hold a massive potential for TGFβR1 inhibition, paving the way for promising future investigations in cancer treatment.

Plume: Efficient and Complete Black-Box Checking of Weak Isolation Levels

Modern databases embrace weak isolation levels to cater for highly available transactions. However, weak isolation bugs have recently manifested in many production databases. This raises the concern of whether database implementations actually deliver their promised isolation guarantees in practice. In this paper we present Plume, the first efficient, complete, black-box checker for weak isolation levels. Plume builds on modular, fine-grained, transactional anomalous patterns, with which we establish sound and complete characterizations of representative weak isolation levels, including read committed, read atomicity, and transactional causal consistency. Plume leverages a novel combination of two techniques, vectors and tree clocks, to accelerate isolation checking. Our extensive assessment shows that Plume can reproduce all known violations in a large collection of anomalous database execution histories, detect new isolation bugs in three production databases along with informative counterexamples, find more weak isolation anomalies than the state-of-the-art checkers, and efficiently validate isolation guarantees under a wide variety of workloads.

Marine Bioactive Molecules as Inhibitors of the Janus Kinases: A Comparative Molecular Docking and Molecular Dynamics Simulation Approach.

A treasure trove of naturally occurring biomolecules can be obtained from sea living organisms to be used as potential antioxidant and anti-inflammatory agents. These bioactive molecules can target signaling molecules involved in the severity of chronic autoimmune diseases such as rheumatoid arthritis (RA). The intracellular tyrosine kinases family, Janus kinases (JAKs, includes JAK1, JAK2, and JAK3), is implicated in the pathogenesis of RA through regulating several cytokines and inflammatory processes. In the present study, we conducted molecular docking and structural analysis investigations to explore the role of a set of bioactive molecules from marine sources that can be used as JAKs' specific inhibitors. Around 200 antioxidants and anti-inflammatory molecules out of thousands of marine molecules found at the Comprehensive Marine Natural Products Database (CMNPD) website, were used in that analysis. The details of the interacting residues were compared to the recent FDA approved inhibitors tofacitinib and baricitinib for data validation. The shortlisted critical amino acids residues of our pharmacophore-based virtual screening were LYS905, GLU957, LEU959, and ASP1003 at JAK1, GLU930 and LEU932 at JAK2, and GLU905 and CYS909 of JAK3. Interestingly, marine biomolecules such as Sargachromanol G, Isopseudopterosin E, Seco-Pseudopterosin, and CID 10071610 showed specific binding and significantly higher binding energy to JAK1 active/potential sites when being compared with the approved inhibitors. In addition, Zoanthoxanthin and Fuscoside E bind to JAK2's critical residues, GLU930 and LEU932. Moreover, Phorbaketal and Fuscoside E appear to be potential candidates that can inhibit JAK3 activity. These results were validated using molecular dynamics simulation for the docked complexes, JAK1(6sm8)/SG, JAK2 (3jy9)/ZAX, and JAK3 (6pjc)/Fuscoside E, where stable and lower binding energy were found based on analyzing set of parameters, discussed below (videos are attached). A promising role of these marine bioactive molecules can be confirmed in prospective preclinical/clinical investigations using rheumatoid arthritis models.

Structural insight into the lead identification of a dual inhibitor of PDE1B and PDE10A: Integrating pharmacophore-based virtual screening, molecular docking, and structure-activity-relationship approaches

Schizophrenia is a chronic neuropsychiatric disorder affecting more than 1% of the world's population. Current antipsychotic treatments show inadequacy in mitigating the negative and cognitive symptoms of schizophrenia. In addition, these medications cause undesirable extrapyramidal side effects. According to the studies, inhibition of phosphodiesterase (PDE) 1B and PDE10A simultaneously can alleviate positive, negative, and cognitive symptoms of schizophrenia. Thus, this study aims to identify new dual inhibitors of PDE1B and PDE10A using ligand-based pharmacophore modelling, virtual screening, and molecular docking studies. Accordingly, the generated pharmacophore models of PDE1B and PDE10A comprised hydrogen bond acceptor, aromatic ring, and hydrophobic features. These features were essential for retrieving the active hits from the Universal Natural Product Database in the virtual screening. Additional filters were subsequently employed to identify potential hits that could be developed into central nervous system-active compounds. Hits meeting all the screening criteria were subjected to docking studies with PDE1B and PDE10A. Among these hits, UNPD167314 exhibited significant binding affinities for the target receptors. It occupied the P-clamp and displayed hydrophobic, aromatic, and hydrogen bond interactions with the active site residues of both receptors, thus selected as a lead compound for the design of potent and selective dual inhibitors. The structural modifications of UNPD167314 resulted in the design of 35 novel inhibitors. Out of 35, four compounds exhibited high and comparable binding affinities for both PDE1B and PDE10A, making them promising candidates for further evaluation and optimisation.

Guiding trust: The role of labeling information in the market for gluten-free pasta (2019–2023)

Labeling transparency is crucial in today's consumer landscape, ensuring informed choices and trust. Food labels are the first piece of information consumers have and become critical when foods must meet dietary restrictions. With its widespread consumption, gluten-free pasta is a fitting model to evaluate labels’ contribution to food literacy. The scope of this study is to examine the clean status and transparency of gluten-free pasta labels in the global marketplace analyzing by ingredient composition, nutritional facts, nutritional claims, and the implementation of quantitative ingredient declarations (QUID). To achieve this, Mintel Global New Product Database (GNPD) was used to retrieve a total of 1188 products sold from 2019 to 2023. Findings revealed variations in gluten-free pasta ingredients, with fresh and dry types varying in nutrients. Branded and private-label pasta differed in salt content, while pulses-based pasta was fiber and protein-rich but pricier. Organic pasta did not consistently show superior qualities, and whole grains did not change nutrition or price. Vegan options were similar in nutrition and price to vegetarian choices. While nutritional claims generally complied with regulations, inconsistent use of QUID highlighted the need for stricter labeling standards to ensure product transparency and support consumer decision-making. Our findings underline the critical role of clear and accurate labeling in empowering consumers and advocating for enhanced regulatory oversight.

Therapeutic effects of natural compounds against diabetic complications via targeted modulation of ferroptosis.

Diabetes mellitus, a chronic metabolic disorder, can result in serious tissue and organ damage due to long-term metabolic dysfunction, leading to various complications. Therefore, exploring the pathogenesis of diabetic complications and developing effective prevention and treatment drugs is crucial. The role of ferroptosis in diabetic complications has emerged as a significant area of research in recent years. Ferroptosis, a recently discovered form of regulated cell death closely linked to iron metabolism imbalance and lipid peroxidation, has garnered increasing attention in studies exploring the potential role of natural products in its regulation. This review provides an overview of the mechanisms underlying ferroptosis, outlines detection methods, and synthesizes information from natural product databases. It also summarizes current research on how natural products may regulate ferroptosis in diabetic complications. Studies have shown that these products can modulate the ferroptosis process by influencing iron ion balance and combating oxidative stress. This highlights the potential of natural products in treating diabetic complications by regulating ferroptosis, offering a new strategy for managing such complications.

Cross-National Analysis of Opioid Prescribing Patterns: Enhancements and Insights from the OralOpioids R Package in Canada and the United States

Background: The opioid crisis remains a significant public health challenge in North America, highlighted by the substantial need for tools to analyze and understand opioid potency and prescription patterns. Methods: The OralOpioids package automates the retrieval, processing, and analysis of opioid data from Health Canada’s Drug Product Database (DPD) and the U.S. Food and Drug Administration’s (FDA) National Drug Code (NDC) database. It includes functions such as load_Opioid_Table, which integrates country-specific data processing and Morphine Equivalent Dose (MED) calculations, providing a comprehensive dataset for analysis. The package facilitates a comprehensive examination of opioid prescriptions, allowing researchers to identify high-risk opioids and patterns that could inform policy and healthcare practices. Results: The integration of MED calculations with Canadian and U.S. data provides a robust tool for assessing opioid potency and prescribing practices. The OralOpioids R package is an essential tool for public health researchers, enabling a detailed analysis of North American opioid prescriptions. Conclusions: By providing easy access to opioid potency data and supporting cross-national studies, the package plays a critical role in addressing the opioid crisis. It suggests a model for similar tools that could be adapted for global use, enhancing our capacity to manage and mitigate opioid misuse effectively.

Snacking insects? A global market investigation

The world population is expected to grow rapidly and exceed 10.4 billion by 2100. In this scenario, greater environmental pressure and natural resource scarcity are inevitable. A possible solution suggested by international authorities is the use of novel protein sources for conventional production, such as the use of edible insects as food, in Western countries. The present work investigates recent market trends in the edible insect sector, in terms of a growing focus on sustainability, product offerings, diversification of insect-based products, and increasing consumer awareness. The Mintel Global New Product Database was used to identify newly launched products in the global market that incorporate insects as ingredients. The market analysis focused on the food category with the highest number of newly launched products, the insect snack bar category. The results of a global market investigation on insect snack bars are further presented including the market analysis of several aspects, such as price, country distribution, nutritional values, and communication strategies. Finally, market considerations are provided that could interest stakeholders in the insect supply chain, including retailers, manufacturers, and policymakers.

Implementing healthy food policies in health sector settings: New Zealand stakeholder perspectives

BackgroundIn 2016, a voluntary National Healthy Food and Drink Policy was released to improve the healthiness of food and drinks for sale in New Zealand health sector organisations. The Policy aims to role model healthy eating and demonstrate commitment to health and well-being of hospital staff and visitors and the general public. This study aimed to understand the experiences of hospital food providers and public health dietitians/staff in implementing the Policy, and identify tools and resources needed to assist with the implementation.MethodsA maximum variation purposive sampling strategy (based on a health district’s population size and food outlet type) was used to recruit participants by email. Video conference or email semi-structured interviews included 15 open-ended questions that focused on awareness, understanding of, and attitudes towards the Policy; level of support received; perceived customer response; tools and resources needed to support implementation; and unintended or unforeseen consequences. Data was analysed using a reflexive thematic analysis approach.ResultsTwelve participants (eight food providers and four public health dietitians/staff) were interviewed; three from small (< 100,000 people), four from medium (100,000-300,000 people) and five from large (> 300,000 people) health districts. There was agreement that hospitals should role model healthy eating for the wider community. Three themes were identified relating to the implementation of the Policy: (1) Complexities of operating food outlets under a healthy food and drink policy in public health sector settings; (2) Adoption, implementation, and monitoring of the Policy as a series of incoherent ad-hoc actions; and (3) Policy is (currently) not achieving the desired impact. Concerns about increased food waste, loss of profits and an uneven playing field between food providers were related to the voluntary nature of the unsupported Policy. Three tools could enable implementation: a digital monitoring tool, a web-based database of compliant products, and customer communication materials.ConclusionsAdopting a single, mandatory Policy, provision of funding for implementation actions and supportive tools, and good communication with customers could facilitate implementation. Despite the relatively small sample size and views from only two stakeholder groups, strategies identified are relevant to policy makers, healthcare providers and public health professionals.

Exploring Natural Compounds as Potential CDK4 Inhibitors for Therapeutic Intervention in Neurodegenerative Diseases through Computational Analysis.

CDK4 is a member of the serine-threonine kinase family, which has been found to be overexpressed in a plethora of studies related to neurodegenerative diseases. CDK4 is one of the most validated therapeutic targets for neurodegenerative diseases. Hence, the discovery of potent inhibitors of CDK4 is a promising candidate in the drug discovery field. Firstly, the reference drug Palbociclib was identified from the available literature as a potential candidate against target CDK4. In the present study, the Collection of Open Natural Products (COCONUT) database was accessed for determining potential CDK4 inhibitors using computational approaches based on the Tanimoto algorithm for similarity with the target drug, i.e., Palbociclib. The potential candidates were analyzed using SWISSADME, and the best candidates were filtered based on Lipinski's Rule of 5, Brenk, blood-brain barrier permeability, and Pains parameter. Further, the molecular docking protocol was accessed for the filtered compounds to anticipate the CDK4-ligand binding score, which was validated by the fastDRH web-based server. Based on the best docking score so obtained, the best four natural compounds were chosen for further molecular dynamic simulation to assess their stability with CDK4. In this study, two natural products, with COCONUT Database compound ID-CNP0396493 and CNP0070947, have been identified as the most suitable candidates for neuroprotection.

A multi-decadal 1 km gridded database of continental-scale spring onset products

The timing of spring onset is a particularly sensitive climate change indicator that also allows the study of weather interannual variations and extremes. This indicator can be derived from a suite of phenological models called the Extended Spring Indices (SI-x). These models transform daily minimum and maximum temperatures into a set of consistent indices that track the timing of first leaf and first bloom for key indicator plant species. The SI-x also enables the calculation of the so-called frost damage index. Using new computational technologies and high spatial resolution gridded weather data, here we present and evaluate a multi-decadal 1 km spatial resolution version of the SI-x models, which cover North American (1980 to 2022) and European areas (1950 to 2020). Because of the generally good agreement with ground phenological observations, this continental-scale and high spatial resolution product can support both scientists and decision makers in their quest to hind- and forecast weather and climate change impacts.

Comparing Nutrient Profiles of Meat and Fish with Plant-Based Alternatives: Analysis of Nutrients, Ingredients, and Fortification Patterns.

Nutrient quality of plant-based meat and fish alternative (MFA) products has been reported as variable. The present objective was to compare the nutrient density of raw meat and fish with MFA products and to examine MFA ingredients and fortification patterns. Nutrient composition data for raw beef, pork, and chicken (n = 450) came from the USDA Standard Reference Legacy Reselase (SR28) nutrient composition database (n = 450). Data for plant-based meat alternatives (n = 118) came from the USDA Branded Food Products Database (BFPDB). Data for fish and seafood (n = 68) and alternatives (n = 12) came from the Danish Frida Database and Mintel (n = 503). Analyses compared macronutrient content and selected micronutrients per 100 g and percentage of US Daily Values. Nutrient density scores were based on the NRF5.3 algorithm. NRF5.3 scores were significantly lower for MFA products as compared to meat or fish. Saturated fat content was lower, but the mean MFA sodium content was 660 mg/100 g compared to 60 mg/100 g for beef. Mean protein content (17 g) was lower than for beef and pork (20 g). A search of ingredient lists found that fortification with most nutrients associated with animal source proteins (such as B vitamins, vitamin D, iodine, zinc, and omega-3 EPA and DHA) was minimal. Plant-based MFA products would benefit from nutrient standards and fortification guidelines to ensure that these products are not nutritionally inferior to the originals.

Identification of Novel PBP2B Protein Inhibitors against Streptococcus pneumoniae in Marine Natural Products using an In-Silico Approach

Background: The aim of this research is to identify marine natural compounds derived from green, red, and brown algae that might possibly inhibit the Penicillin-Binding Proteins (PBPs) protein, which is responsible for the development of antibiotic resistance in Streptococcus pneumoniae (mutated resistant 5204-PBP2B strain). We obtained this by using virtual screening and molecular docking. In AutoDock Vina and the Schrodinger suite software, we screened a library of marine natural chemicals and discovered four intriguing candidates that had strong binding affinities to the active region of the PBPs protein. Based on our findings, four naturally occurring marine chemicals show great promise as new inhibitors of S. pneumoniae 5204-PBP2B protein. These discoveries reveal important new information on the potential application of marine natural products as a source of new drugs to combat antibiotic resistance in Streptococcus pneumoniae and other bacterial infections. Methods: The 3318 compounds in the Comprehensive Marine Natural Products Database (CMNPD) derived from green algae (293 compounds), brown algae (1212 compounds) and red algae (1813 compounds) were taken into consideration for this study. Through virtual screening and molecular docking investigations, we found the optimum compounds for the Penicillin-Binding Proteins (PBPs) protein in Streptococcus pneumoniae. Utilizing AutoDock Vina and Schrodinger Suite software, the 5204-PBP2B protein selected for this investigation was examined. The structure and binding interaction have been displayed using PyMOL software. Results: Through virtual screening and molecular docking investigations for the 5204-PBP2B protein in Streptococcus pneumoniae, we were able to identify four marine natural products that are present in brown algae from the Comprehensive Marine Natural Products Database. Conclusion: The study has indicated that the main cause of bacterial resistance to antibiotics is 5204-PBP2B in S. pneumoniae. This study's methodology has been shown to be effective in identifying four strong inhibitors of the CMNPD. In this work, potent molecules from CMNPD compounds were screened using the 3D structure of mutated resistant 5204 strain, named 5204- PBP2B (PDB ID: 2WAE) of S. pneumoniae. Out of 3318 compounds that showed strong interactions with PBP2B, docking studies revealed that four of the compounds were inhibitory for the protein and could be used to treat PBP2B. These four marine products were selected as a result of our earlier research on Klebsiella pneumonia’s New Delhi metallo-β-lactamase-1 (NDM-1) protein. This study thus reveals the importance of marine natural products for improving the drug development process, as well as the ability of four marine products generated from brown algae to inhibit both the NDM-1 protein of Klebsiella pneumoniae and the 5204-PBP2B protein in Streptococcus pneumoniae. It is also possible to expand this approach by investigating how different receptor inhibitors interact in a lab setting. Potential inhibitors can be discovered by evaluating the biological activity of the drugs and applying virtual screening and molecular docking techniques.

Natural Products from Brazilian Biodiversity Explored as Anti-EBV Drug Candidates: In-Silico Database Mining, Docking Computations, Molecular Dynamics and DFT Calculations

A DNA tumor virus called Epstein–Barr virus (EBV) is the cause of 1–2% of human cancers. EBV-associated carcinogenesis is caused by a persistent latent infection. The shortage of antiviral medications or vaccinations to control the virus led to a significant percentage of critically sickness individuals needing to be hospitalized. In the absence of an effective vaccine and approved drug, there is an immediate need for treatments that can combat EBV infection. Epstein–Barr nuclear antigen 1 (EBNA1) is continually expressed in all malignancies linked to EBV; it is a desirable target for curative interference. Herein, natural product compounds from the Nuclei of Bioassays, Ecophysiology and Biosynthesis of Natural Products (NuBBE) database were mined to identify potent EBNA1 inhibitors. The performance of the molecular docking technique was initially assessed in expecting the ligand-target binding pose according to the available experimental data. On the basis of the estimated docking protocol, the NuBBE database was virtually screened toward the EBNA1 protein, and the natural compounds with binding scores less than KWG (calc. -7.8 kcal/mol) were subjected to molecular dynamics (MD) simulations followed by binding energy ([Formula: see text] calculation using MM/GBSA approach. Based on binding energy computations, NuBBE1460 revealed superior [Formula: see text] with a value of −36.2 kcal/mol, compared to KWG (calc. -32.4 kcal/mol). Post-MD analyses displayed a high steadiness of NuBBE1460 within the EBNA1 protein binding pocket. Furthermore, the physicochemical, pharmacokinetic and toxicity features of the identified compound were predicted, demonstrating high degrees of its oral bioavailability. The energetical and geometrical properties of NuBBE1460 were calculated using the DFT method. Conclusively, this study offers NuBBE1460 obtained from natural sources as a lead EBNA1 inhibitor for future investigation and development as a therapeutic for EBV.

Interlinking environmental and food composition databases: An approach, potential and limitations

Connecting entries from environmental and nutritional databases of food products is needed to identify sustainable food options. To overcome the hurdle for a successful data standardization, this paper aimed to explore the general structure of food composition and life cycle inventory (LCI) databases and to provide a semi-automatized approach on how to successfully interlink data of two example databases.The structure, the data availability and accessibility of food entries (FI) from the LCI database Agribalyse and selected food composition EuroFIR databases were analyzed. Harmonized food names from LanguaL™ codes from food classification systems were gathered and validated manually in order to use as descriptors to tag database entries in an automated way.Both databases, EuroFIR and Agribalyse, provided sufficient amount of meta data to interlink FI with the standardization approach proposed. Information on food name, food specification, food processing and the type of production was used for data interlinkage purposes. Manual validation of data interlinkage showed that two out of a sample of 54 entries were found to have incorrectly assigned descriptors.Agreeing on common principles (e.g., use of a specific classification system, common database formats) and improving meta data availability would facilitate database interlinkage and improve both, accuracy and efficiency. Developing solutions to increase meta data availability and accessibility of FI in food databases should become a key area of research in order to transition into more reliable database connection systems.

Hybrid Virtual Screening Approach to Predict Novel Natural Compounds against HIV-1 CCR5.

Human immunodeficiency virus (HIV) infection continues to pose a major global health challenge. HIV entry into host cells via membrane fusion mediated by the viral envelope glycoprotein gp120/gp41 is a key step in the HIV life cycle. CCR5, expressed on CD4+ T cells and macrophages, acts as a coreceptor facilitating HIV-1 entry. The CCR5 antagonist maraviroc is used to treat HIV infection. However, it can cause adverse effects and has limitations such as only inhibiting CCR5-tropic viruses. There remains a need to develop alternative CCR5 inhibitors with improved safety profiles. Natural products may offer advantages over synthetic inhibitors including higher bioavailability, binding affinity, effectiveness, lower toxicity, and molecular diversity. However, screening the vast chemical space of natural compounds to identify novel CCR5 inhibitors presents challenges. This study aimed to address this gap through a hybrid ligand-based pharmacophore modeling and molecular docking approach to virtually screen large natural product databases. A reliable pharmacophore model was developed based on 311 known CCR5 antagonists and validated against an external data set. Five natural product databases containing over 306,000 compounds were filtered based on drug-likeness rules. The validated pharmacophore model screened the databases to identify 611 hits. Key residues of the CCR5 receptor crystal structure were identified for docking. The top hits were docked, and interactions were analyzed. Molecular dynamics simulations were conducted to examine complex stability. Computational prediction evaluated pharmacokinetic properties. Three compounds exhibited similar interactions and binding energies to maraviroc. MD simulations demonstrated complex stability comparable to maraviroc. One compound showed optimal predicted absorption, minimal metabolism, and a lower likelihood of interactions than maraviroc. This computational screening workflow identified three natural compounds with promising CCR5 inhibition and favorable pharmacokinetic profiles. One compound emerged as a lead based on bioavailability potential and minimal interaction risk. These findings present opportunities for developing alternative CCR5 antagonists and warrant further experimental investigation. Overall, the hybrid virtual screening approach proved effective for mining large natural product spaces to discover novel molecular entities with drug-like properties.

Reasons why life on Earth rarely makes fluorine-containing compounds and their implications for the search for life beyond Earth

Life on Earth is known to rarely make fluorinated carbon compounds, as compared to other halocarbons. We quantify this rarity, based on our exhaustive natural products database curated from available literature. We build on explanations for the scarcity of fluorine chemistry in life on Earth, namely that the exclusion of the C–F bond stems from the unique physico-chemical properties of fluorine, predominantly its extreme electronegativity and strong hydration shell. We further show that the C–F bond is very hard to synthesize and when it is made by life its potential biological functions can be readily provided by alternative functional groups that are much less costly to incorporate into existing biochemistry. As a result, the overall evolutionary cost-to-benefit balance of incorporation of the C–F bond into the chemical repertoire of life is not favorable. We argue that the limitations of organofluorine chemistry are likely universal in that they do not exclusively apply to specifics of Earth’s biochemistry. C–F bonds, therefore, will be rare in life beyond Earth no matter its chemical makeup.