Potential Interactions Research Articles

Comprehensive In Silico Analysis of Uncaria Tomentosa Extract: Chemical Profiling, Antioxidant Assessment, and CLASP Protein Interaction for Drug Design in Neurodegenerative Diseases.

Uncaria tomentosa is a traditional medicinal herb renowned for its anti-inflammatory, antioxidant, and immune-enhancing properties. In the realm of neurodegenerative diseases (NDDS), CLASP proteins, responsible for regulating microtubule dynamics in neurons, have emerged as critical players. Dysregulation of CLASP proteins is associated with NDDS, such as Alzheimer's, Parkinson's, and Huntington's diseases. Consequently, comprehending the role of CLASP proteins in NDDS holds promise for the development of innovative therapeutic interventions. The objectives of the research were to identify phytoconstituents in the hydroalcoholic extract of Uncaria tomentosa (HEUT), to evaluate its antioxidant potential through in vitro free radical scavenging assays and to explore its potential interaction with CLASP using in silico molecular docking studies. HPLC and LC-MS techniques were used to identify and quantify phytochemicals in HEUT. The antioxidant potential was assessed through DPPH, ferric reducing antioxidant power (FRAP), nitric oxide (NO) and superoxide (SO) free radical scavenging methods. Interactions between conventional quinovic acid, chlorogenic acid, epicatechin, corynoxeine, rhynchophylline and syringic acid and CLASP were studied through in silico molecular docking using Auto Dock 4.2. The HEUT extract demonstrated the highest concentration of quinovic acid derivatives. HEUT exhibited strong free radical-scavenging activity with IC50 values of 0.113 μg/ml (DPPH) and 9.51 μM (FRAP). It also suppressed NO production by 47.1 ± 0.37% at 40 μg/ml and inhibited 77.3 ± 0.69% of SO generation. Additionally, molecular docking revealed the potential interaction of quinovic acid with CLASP for NDDS. The strong antioxidant potential of HEUT and the interaction of quinovic acid with CLASP protein suggest a promising role in treating NDDS linked to CLASP protein dysregulation.

Investigation of mono-nuclear cobalt(II) complexes with a tri-dentate quinoxalyl-hydrazone ligand for their potential in biological research and interaction with ct-DNA.

The condensing reaction of 2-hydroxy-1-naphthaldehyde with quinoxalyl-2-carbohydrazide resulted in synthesizing of a novel derivative of hydrazone quinoxalyl ligand (H2dpq). The bonding behavior between H2dpq and Co(II) ion was investigated in molar ratios of 1: 1 and 2: 1 to produce two different complexes, Codpq and Co(dpq)2, respectively. Their chemical structure was verified using several spectroscopic approaches. The characterization envolved micro-C, H, and N-elemental analyses, thermogravimetric investigations, as well as the examination of their magnetic and conductance properties. The inhibitory effects of H2dpq (the free ligand) and its Co(II)-chelates on the growing up of three specific bacterial series, three specific fungal series, and three famous human cancer cell lines were evaluated based on their structure features. The study referred to the pivotal function of Co(II) and its ratio in the two complexes. The antioxidant activity was determined for all current compounds within DPPH and SOD assays, reporting respectable antioxidant reactivity. The interaction of H2dpq, Codpq, and Co(dpq)2 with calf thymus DNA (ct-DNA) was assessed by analyzing through the alterations in the viscometric and spectrophotometric properties. Determination of binding constant (Kb, 13.12, 16.02, and 16.82×107mol-1dm3), Gibb's free energy (∆Gb≠, were -40.21, -46.13, and -46.67kJmol-1), and the chromism mode (hypo-character) were employed for H2dpq, Codpq, and Co(dpq)2 to assess the interactive modes, respectively. Rewardingly, the monometallic-chelates Co(II)-complexes displayed modified binding action more than that of H2dpq against ct-DNA.

Assessment of Potential Drug-Drug Interactions for Novel Oral Melanocortin-1 Receptor Agonist Dersimelagon.

Dersimelagon is a novel investigational orally administered selective agonist of the melanocortin-1 receptor. The drug-drug interaction (DDI) potential of dersimelagon was investigated in both nonclinical (in vitro) and clinical studies. The invitro inhibition of CYP/UGT isoforms and efflux/uptake transporters by dersimelagon was assessed. The impact of 300-mg dersimelagon on the pharmacokinetics (PK) of substrate drugs and the effect of co-administering verapamil on 100-mg dersimelagon PK (as substrate drug) were investigated in healthy participants in a Phase 1 study. DDIs were assessed based on ratios of Cmax and AUC0-∞ of substrate drug administered alone and with dersimelagon (or verapamil). Relatively potent invitro inhibition of CYP2C9, CYP3A, UGT1A1, BCRP, P-gp, and OATPs by dersimelagon was observed. In the clinical study, exposures of atorvastatin (CYP3A, P-gp, BCRP, OATP substrate) rosuvastatin (BCRP and OATP substrate), and β-hydroxy simvastatin (metabolite of simvastatin) increased 2- to 3-fold (atorvastatin: Cmax LS mean ratio = 198.0%; AUC0-∞ ratio = 196.6%; rosuvastatin: Cmax ratio = 316.5%, AUC0-∞ ratio = 206.0%) when co-administered with dersimelagon. Midazolam (CYP3A substrate), digoxin (P-gp), pravastatin (OATP), and simvastatin (CYP3A) did not show any clinically relevant DDI effects when co-administered with dersimelagon. Dersimelagon exposure increased ~25% when co-administered with verapamil, an effect not considered clinically relevant. Dersimelagon 300 mg did not elicit major DDIs involving CYP/UGT enzymes and drug transporters; however, dersimelagon may have potential for clinically relevant DDIs with drugs that are substrates for BCRP, such as atorvastatin and rosuvastatin, and caution should be exercised when co-administering 300-mg dersimelagon with these statin drugs. Trial Registration: ClinicalTrials.gov: NCT04793295, NCT04402489, NCT04440592, NCT02834442, NCT03520036, NCT03503266.

Atomistic assessment of interfacial interaction potential in tungsten twist grain boundaries

Atomistic assessment of interfacial interaction potential in tungsten twist grain boundaries

Clinical Evaluation of Drug-Drug Interactions with Obeldesivir, an Orally Administered Antiviral Agent.

Obeldesivir is an oral nucleoside analog prodrug inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase and other viral polymerases. Here, two Phase I studies evaluated potential drug-drug interactions between obeldesivir and substrates or inhibitors of cytochrome P450 and drug transporters in healthy participants. When obeldesivir was tested as a precipitant, pharmacokinetic parameter point estimates for midazolam (CYP3A4 inhibition/induction), caffeine (CYP1A2 inhibition), and metformin (organic cation transporter 1 inhibition) exposures were within 80-125% no-effect bounds representing the interval within which a systemic exposure change does not warrant clinical action based on EMA/FDA guidance. Dabigatran (P-glycoprotein substrate) and pitavastatin (organic anion transporting polypeptide 1B1/1B3 substrate) exposures decreased by approximately 25% and 30%, respectively, with obeldesivir coadministration; these were considered not clinically relevant, as these exposure changes are not associated with dose changes or precautions in the US prescribing information for these drugs. When obeldesivir was evaluated as an object, exposures of GS-441524, the parent nucleoside monophosphate metabolite of obeldesivir, were within the 80-125% no-effect bounds for ritonavir (P-glycoprotein inhibition) and cyclosporin A (breast cancer resistance protein inhibition) coadministration. Famotidine (gastric acid suppression) coadministration decreased GS-441524 exposure by approximately 26%; this was within the range of exposures observed in previous Phase III studies and was considered not clinically relevant. Obeldesivir was well tolerated, and adverse events were mild to moderate. These findings indicate that obeldesivir has low potential for drug-drug interactions. Obeldesivir remains a promising treatment against a broad spectrum of viruses given its antiviral activity and favorable safety profile.

Single-Site Local-Density Potentials for the Mesoscopic Representation of Water Based on the SAFT-VR Mie Equation of State.

In this article, we present three mesoscopic models for water. All three models make use of local density-dependent interaction potentials, as employed within the Pagonabarraga-Frenkel framework [Pagonabarraga, I.; Frenkel, D. J. Chem. Phys. 2001, 115, 5015-5026]. The forms of these three interaction potentials are based on the free energy function of the SAFT-VR Mie equation of state (EoS) [Lafitte, T. J. Chem. Phys. 2013, 139, 154504]. Two of these models represent the water-water interaction as a spherically symmetric Mie interaction with temperature-dependent parameters, while the third model works with a temperature-independent Mie potential, but then explicitly models the effect of hydrogen bonding. All three models provide good predictions of the vapor-liquid equilibrium of water over a wide temperature range. They also give accurate predictions of the isothermal compressibility for both sub- and supercritical conditions. To model the interfacial tension of the vapor-liquid interface with our mesoscale simulations, we added a square-gradient term to our potential energy function. We show that the addition of this term has a minimal effect on the bulk properties of water. However, by parametrizing the coefficient of this term as a function of temperature, all three models again provide excellent predictions of water's interfacial tension over a wide temperature range. Of the three models, our preference is for the model that includes an association term, as this model can operate successfully over a wider range of conditions.

Closed-channel parameters of Feshbach resonances

This work investigates how the closed channel of a Feshbach resonance is characterised by experimental observables. Surprisingly, it is found that the two-body observables associated with the Feshbach resonance can be insensitive to the properties of the closed channel. In particular, it is impossible in this situation to determine the energy of the bound state causing the resonance from the usual experimental data. This is the case for all magnetic Feshbach resonances in ultracold atoms, due to their deep two-body interaction potentials. This insensitivity highlights a major difference with Feshbach resonances that involve shallow interaction potentials, such as hadron resonances. It appears however that short-range two-body correlations and three-body observables are affected by a parameter of the closed channel called the “closed-channel scattering length”. A photoassociation experiment is proposed to measure this parameter in ultracold atom systems.

P-1063. SCY-247: A Second-generation IV/Oral Triterpenoid Antifungal with Extensive Tissue Distribution and Pharmacokinetics, and Low Drug-Drug Interaction Potential

Abstract Background SCY-247 is an IV/oral second-generation triterpenoid anti-fungal for systemic fungal infections including multidrug resistant pathogens. Here we present translational data for nonclinical pharmacokinetics (PK) including dose-related tissue disposition in a murine C. glabrata model and correlation to reductions in fungal burden. Further, in vitro CYP450 interactions were evaluated to assess potential for clinical drug-drug interactions (DDIs). Methods The PK of SCY-247 was determined in rats and dogs. Plasma and tissue exposures were compared to reductions in kidney and lung fungal burden in a model of invasive C. glabrata. Neutropenic mice were infected IV with C. glabrata (∼108 yeast cells/mouse) and sacrificed on Day +7. Potential for inhibiting or inducing CYP450 isoforms was assessed in vitro using methods supportive of an FDA Investigational New Drug (IND) Application. Results SCY-247 has low clearance (∼10% liver blood flow) with half-life ≥15 hours following oral and IV administration to rat and dog consistent with once-daily administration in humans. Volume of distribution is ∼3 L/kg supportive of extensive tissue distribution. Exposure increased on repeat administration. Solubility of oral SCY-247 as a salt is >30 mg/mL at gastric pH consistent with rapid dissolution in the stomach and rapid absorption - as demonstrated by an early Tmax (0.5-2hr) following oral administration. In a murine model of C. glabrata infection, SCY-247 demonstrated dose-related increases in exposure and corresponding reduction in fungal burden (right figure panel) with higher distribution in kidney and lung tissue compared to plasma (left figure panel). In vitro, SCY-247 did not induce human CYP450s 1A2, 2B6 or 3A4. The IC50 values for inhibition of human 2C9, 2C19 and 3A isoforms were >20 μM ( >10-fold higher than the anticipated clinical Cmax) supportive of low risk of DDI’s for these isoforms. Conclusion SCY-247 has demonstrated dose- and tissue-related exposure reductions in fungal burden, PK consistent with once daily dosing to humans and low risk for CYP450-related DDIs. Disclosures Steve Wring, PhD, SCYNEXIS, Inc.: Advisor/Consultant Katyna Borroto-Esoda, MS, Scynexis Inc: Advisor/Consultant Nathan P. Wiederhold, PharmD, BioMerieux: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mycovia: Grant/Research Support|Scynexis: Grant/Research Support|Sfunga: Grant/Research Support David A. Angulo, MD, SCYNEXIS, Inc.: Board Member|SCYNEXIS, Inc.: SCYNEXIS, INC Officer and Board Member, SCYNEXIS Patents|SCYNEXIS, Inc.: Stocks/Bonds (Public Company)

P-555. Use of Long-Acting Cabotegravir/Rilpivirine in People Living with HIV with Renal Transplantation

Abstract Background Cabotegravir/Rilpivirine (CAB/RPV) represents a novel combination of long-acting injectable antiretroviral therapy (LAIART). Although the unique benefits of LAIART have been demonstrated in large clinical trials among people with HIV, including a favorable safety profile, few drug-drug interactions, and viral control without a daily oral pill requirement, evidence of LAIART use among PWH diagnosed with end-stage chronic kidney disease (CKD) and during kidney transplantation (KT) remains sparse. Detailed timeline of all 3 patients in the study. Methods A phase IV clinical trial CAPRI (NCT05601128) was designed to evaluate the pharmacokinetics and safety of long-acting CAB/RPV among PWH with CKD >= stage 4 or ongoing hemodialysis. Three enrolled participants were included, in this analysis because of their KT status, of them, one KT before the trial and two KT during the trial. The peri- and post-operative effects of CAB/RPV LA were evaluated focusing on viral load, CD4+ counts, and potential drug interactions. According to protocol, CAB/RPV PK samples were obtained and planned to be measured and analyzed. Results All three participants have been virally suppressed (< 50 copies/ml) by CAB/RPV LA with stable CD4+ counts while maintaining appropriate graft function during 12months of study period. The timeline for each participant was depicted in the Figure and details were summarized in terms of virologic and immunologic outcomes as well as renal function at different study periods. CAB/RPV LA was well tolerated, without major related adverse events noted. The renal function was significantly improved, dialysis free, in two participants receiving KT during the trial whereas it remained stable, dialysis free, in the participant with prior KT. The reported tacrolimus trough concentrations were maintained within the therapeutic range to protect the graft function. Conclusion The safety and efficacy of CAB/RPV LA have been observed in these participants, supporting its potential use among those with severe renal impairment and kidney transplantation. Additional advantages including lack of adherence barriers and low drug interaction potential are likely to increase viral suppression and improve overall quality of life in this special population. Disclosures Chiu-bin hsiao, MD, Viiv, Gilead: Grant/Research Support

Conservation of OFD1 Protein Motifs: Implications for Discovery of Novel Interactors and the OFD1 Function

OFD1 is a protein involved in many cellular processes, including cilia biogenesis, mitotic spindle assembly, translation, autophagy and the repair of double-strand DNA breaks. Despite many potential interactors identified in high-throughput studies, only a few have been directly confirmed with their binding sites identified. We performed an analysis of the evolutionary conservation of the OFD1 sequence in three clades: 80 Tetrapoda, 144 Vertebrata or 26 Animalia species, and identified 59 protein-binding motifs localized in the OFD1 regions conserved in various clades. Our results indicate that OFD1 contains 14 potential post-translational modification (PTM) sites targeted by at least eight protein kinases, seven motifs bound by proteins recognizing phosphorylated aa residues and a binding site for phosphatase 2A. Moreover, OFD1 harbors both a motif that enables its phosphorylation by mitogen-activated protein kinases (MAPKs) and a specific docking site for these proteins. Generally, our results suggest that OFD1 forms a scaffold for interaction with many proteins and is tightly regulated by PTMs and ligands. Future research on OFD1 should focus on the regulation of OFD1 function and localization.

Structural evolution of particle configurations: Zero-temperature phases under increasing confinement.

In this study, we investigate the phase behavior and structural organization of colloidal particles in a two-dimensional (2D) system under isotropic harmonic confinement using overdamped Langevin dynamics simulations. We employ a modified mermaid potential, which introduces an additional short-distance term resulting in a null-force region, distinct from the conventional mermaid potential. This modification facilitates a richer exploration of self-assembled structures, revealing a variety of phases influenced by the interplay between confinement strength V0 and the interaction potential. Our analysis spans a wide range of parameters, resulting in a detailed phase diagram that captures transitions from dispersed clusters to well-ordered patterns, including square, triangular, rhomboidal, and mixed configurations, as the confinement strength increases. The findings underscore the intricate balance of forces governing the self-assembly of colloidal systems and offer valuable insights for future experimental realizations.

Implications of frequent hitter E3 ligases in targeted protein degradation screens.

Targeted protein degradation (TPD) offers a promising approach for chemical probe and drug discovery that uses small molecules or biologics to direct proteins to the cellular machinery for destruction. Among the >600 human E3 ligases, CRBN and VHL have served as workhorses for ubiquitin-proteasome system-dependent TPD. Identification of additional E3 ligases capable of supporting TPD would unlock the full potential of this mechanism for both research and pharmaceutical applications. This perspective discusses recent strategies to expand the scope of TPD and the surprising convergence of these diverse screening efforts on a handful of E3 ligases, specifically DCAF16, DCAF11 and FBXO22. We speculate that a combination of properties, including superficial ligandability, potential for promiscuous substrate interactions and high occupancy in Cullin-RING complexes, may position these E3 ligases as 'low-hanging fruit' in TPD screens. We also discuss complementary approaches that might further expand the E3 ligase landscape supporting TPD.

A Survey on WiFi-based Human Identification: Scenarios, Challenges, and Current Solutions

With the evolution of wireless sensing technology, WiFi-based human identification has demonstrated tremendous potential in human-computer interaction and home security. However, most existing research operates in controlled environments, overlooking the complexities of real-world scenarios, such as signal fading, signal interference and uncertainty, and the diversity of application requirements. This article presents a comprehensive analysis of a series of representative research articles on WiFi-based human identification and summarizes five major challenges in achieving high-precision identification in complex application scenarios. Non-line-of-sight (NLOS) user sensing, coexistence user sensing, dynamic group user sensing, cross-domain user sensing, and multi-task sensing. Additionally, this article proposes a series of current solutions, including improving the signal-to-noise ratio (SNR) of NLOS sensing from the perspective of communication signals and sensing models, addressing coexistence sensing issues, designing adaptable tasks for dynamic user groups, leveraging techniques like adversarial learning and transfer learning for cross-domain problems, and employing modular deep learning architectures. By providing a comprehensive overview of WiFi-based human identification, this survey not only offers insights into current research but also charts a roadmap for future investigations. It is anticipated that this survey will stimulate innovative research endeavors and foster the expansion of wireless sensing technology across diverse application domains.

Navigating through chemometrics: Unveiling antibiotic-food interactions for improved pediatric formulations ahead.

Given the challenges of pediatric antibacterial therapy, it is crucial to formulate antibiotics with a lower potential for interaction with dietary interventions and tailor them for optimal administration in children. Chemometric methods allow us to analyze multiple interrelated variables simultaneously and uncover correlations. We applied a chemometric approach to examine how food, beverages, antacids, and mineral supplements affect antibiotic bioavailability in adults and children, aiming to explore relationships between antibiotic structure, physicochemical properties, and post-meal changes in pharmacokinetic (PK) parameters. We selected 95 antibacterial drugs for analysis, including beta-lactams (32), quinolones (25), macrolides (13), tetracyclines (16), and others (9). The input dataset comprised information from published clinical trials, chemical records, and calculations. We constructed hierarchical partial least squares (PLS) models with changes in PK parameters (ΔAUC, ΔCmax, ΔTmax, and Δ t ½) as response parameters and nine groups of molecular descriptors (M1-M9) as predictor parameters. We performed analyses separately in children and adults for different dietary interventions. In the final 10 PLS models, significant components explained 61-90% and 10.3-54.4% of the variance in the predictor and response parameter sets, respectively. We obtained 59 significant positive and negative correlations between antibiotic structure or physicochemical properties (molecular descriptors) and action in the human body in the presence of food, antacids, or mineral supplements (changes in PK parameters), of which 41 concern pediatric patients. Chemometric methods can be helpful and valuable in investigating the interactions between antibiotics and dietary interventions. Using chemometrics may pave the way for formulating antibiotics for children with a lower potential to interact with food.

Finite-size effects of the excess entropy computed from integrating the radial distribution function

Computation of the excess entropy S ex from the second-order density expansion of the entropy holds strictly for infinite systems in the limit of small densities. For the reliable and efficient computation of S ex it is important to understand finite-size effects. Here, expressions to compute S ex and Kirkwood–Buff (KB) integrals by integrating the Radial Distribution Function (RDF) in a finite volume are derived, from which S ex and KB integrals in the thermodynamic limit are obtained. The scaling of these integrals with system size is studied. We show that the integrals of S ex converge faster than KB integrals. We compute S ex from Monte Carlo simulations using the Wang–Ramírez–Dobnikar–Frenkel pair interaction potential by thermodynamic integration and by integration of the RDF. We show that S ex computed by integrating the RDF is identical to that of S ex computed from thermodynamic integration at low densities, provided the RDF is extrapolated to the thermodynamic limit. At higher densities, differences up to 20 % are observed.

Segregation of Factors Leading to Temperature-Dependent Ion Transport in Mixed Cationic Systems in Cation Exchange Membranes.

This study delves into the interplay of temperature, composition, tortuosity, and electrostatic interactions on ion diffusion within cation exchange membranes. It explores the temperature dependence (16-60 °C) of the self-diffusion coefficients (SDCs) of Ba2+ and Eu3+ ions within the Nafion 117 cation exchange membrane, particularly in the presence of Na+ ions. Radiotracer techniques and electrochemical impedance spectroscopy were employed to investigate these SDCs. Significant differences were observed between the SDCs of Ba2+ and Eu3+ ions in both monoionic (only Na+, Ba2+, or Eu3+) and binary (Ba2+-Na+ and Eu3+-Na+) systems. Temperature-induced reduction in water uptake was probed by the gravimetric as well as 3H radiotracer techniques for the first time, and the effect of the tortuosity factor on ion diffusion was understood. This enabled quantification of the electrostatic interaction factor as a function of temperature, revealing a decreasing trend with increasing temperature in both mono- and binary systems. An attempt was also made to correlate the activation energy (Arrhenius-type plots) and the net interaction potential within this temperature range. The findings indicate that ion diffusion is primarily influenced by electrostatic interaction, especially for multivalent ions, while tortuosity plays a negligible role in determining the overall diffusion trend.

Evaluating ion dynamics through Coulomb and Yukawa interaction potentials in one-component strongly coupled plasmas

Evaluating ion dynamics through Coulomb and Yukawa interaction potentials in one-component strongly coupled plasmas

PROTCROWN: A Manually Curated Resource of Protein Corona Data for Unlocking the Potential of Protein-Nanoparticle Interactions.

The emergence of the "Protein Corona" is a pivotal concept in bioinformatics and nanotechnology, crucial for understanding nanomedicine delivery and nanoparticle-biological entity interactions. After entering a biological fluid, such as blood, nanoparticles (NPs, such as nanomedical carriers) are quickly coated with proteins, forming a protein interface layer called the protein corona. An in-depth investigation into the protein corona is essential for elucidating the biological ramifications of NPs and their prospective applications within the medical field and beyond. To advance our understanding of the intricate interactions between NPs and biological systems, we have developed PROTCROWN, the inaugural protein corona database. This resource systematically curates and organizes data relevant to the protein corona, facilitating advanced analysis and research in the field. It provides a convenient data query platform for researchers and supports data visualization and analysis. Our database, PROTCROWN, is accessible at http://www.protcrown.cn.

Dynamical arrest for globular proteins with patchy attractions.

Attempts to use colloid science concepts to better understand the dynamic properties of concentrated or crowded protein solutions are challenging due to the fact that globular proteins generally have heterogeneous surfaces that result in anisotropic or patchy contributions to their interaction potential. This is particularly difficult when targeting non-equilibrium transitions such as glass and gel formation in concentrated protein solutions. Here we report a systematic study of the reduced zero shear viscosity ηr of the globular protein γB-crystallin, an eye lens protein that plays a vital role in vision-related phenomena such as cataract formation or presbyopia, and compare the results to the existing structural and dynamic data. Combining two different tracer particle-based microrheology methods allows us to precisely locate the line of kinetic arrest within the phase diagram and characterize the functional form of the concentration and temperature dependence of ηr. We show that while our results qualitatively confirm the existing view that this protein can be reasonably well described using a coarse-grained picture of a patchy colloid with short range attractions, there are a number of novel findings that cannot easily be understood with the existing simple colloid models. We demonstrate in particular the complete failure of an extended law of corresponding states for a description of the temperature dependence of the arrest line, and discuss the role that transient clusters play in this context.

USE OF CULTURAL HERITAGE IN THE HOTEL AND RESTAURANT SPHERE OF TOURISM: FROM THE HISTORY OF THE EUROPEAN EXPERIENCE

The use of European monuments of cultural heritage in the hotel and restaurant sector of tourism is annualized in the article. Cultural heritage properties that have been repurposed as restaurants and hotels offer visitors a unique blend of history and modern comfort. Adaptive reuse of monuments of cultural significance as hotel-restaurant-type facilities allows the repurposing of existing buildings fornew functions while preserving their architectural and cultural value. In this way, historical buildings are preserved and, at the same time, we get a new tourist product that meets the modern tourist's cultural, educational, and tourist needs. The tourism potential of such interactions has been revealed. This is the cultural immersion of the tourist in a certain historical atmosphere, and promotion of economicdevelopment of the region, preservation of cultural heritage, popularization of local cultural and culinary traditions, educational and educational activities. Hotels located near or within historic sites can offer educational programs, tours, and cultural activities that give tourists insight into the history, architecture, and significance of the site. These initiatives contribute to the intellectual enrichment of the tourists and contribute to a deeper appreciation of the cultural heritage of the destination country. The use of monuments of historical and cultural significance in the hotel and restaurant tourism sector not only improves the experience of visitors but also contributes to the preservation of cultural heritage, economic development,promotion of sustainable tourism practices, educational opportunities, andbranding of destinations.