Efficient Binding Research Articles

Analysis of Methylesterase Gene Family in Fragaria vesca Unveils Novel Insights into the Role of FvMES2 in Methyl Salicylate-Mediated Resistance against Strawberry Gray Mold.

Methylesterases (MESs) hydrolyze carboxylic ester and are important for plant metabolism and defense. However, the understanding of MES' role in strawberries against pathogens remains limited. This study identified 15 FvMESs with a conserved catalytic triad from the Fragaria vesca genome. Spatiotemporal expression data demonstrated the upregulated expression of FvMESs in roots and developing fruits, suggesting growth involvement. The FvMES promoter regions harbored numerous stress-related cis-acting elements and transcription factors associated with plant defense mechanisms. Moreover, FvMES2 exhibited a significant response to Botrytis cinerea stress and showed a remarkable correlation with the salicylic acid (SA) signaling pathway. Molecular docking showed an efficient binding potential between FvMES2 and methyl salicylate (MeSA). The role of FvMES2 in MeSA demethylation to produce SA was further confirmed through in vitro and in vivo assays. After MeSA was applied, the transient overexpression of FvMES2 in strawberries enhanced their resistance to B. cinerea compared to wild-type plants.

Inhibition of RNA Phosphodiester Backbone Cleavage in the Presence of Organic Cations of Different Sizes.

Living cells contain various types of organic cations that may interact with nucleic acids.In order to understand thenucleic acid-binding properties oforganic cations of different sizes, we investigated the ability ofsimple organic cations to inhibit the RNA phosphodiester bond cleavage promoted by Mg2+, Pb2+, and RNA-cleaving serum proteins. Kinetic analysis using chimeric DNA-RNA oligonucleotides showed that the cleavage at ribonucleotide sites was inhibited in the presence of monovalent cations comprising alkyl chains or benzene rings. The comparison of thecleavage rates in the presence ofquaternary ammonium and phosphonium ionsindicated thatthe steric hindrance effect of organic cations on their binding tothe RNA backboneis significant when the cation size is larger than the phosphate-phosphate distance of a single-stranded nucleic acid.The cleavage inhibition was also observed for ribonucleotides located in long loops but not in short loopsof oligonucleotide structures, indicating less efficient binding of bulky cationsto structurally constrained regions.Theseresults revealtheunique nucleic acid-binding properties of bulky cations distinct from those of metal ions.

Radiological and Molecular Analysis of Radioiodinated Anastrozole and Epirubicin as Innovative Radiopharmaceuticals Targeting Methylenetetrahydrofolate Dehydrogenase 2 in Solid Tumors

In the dynamic field of radiopharmaceuticals, innovating targeted agents for cancer diagnosis and therapy is crucial. Our study enriches this evolving landscape by evaluating the potential of radioiodinated anastrozole ([125I]anastrozole) and radioiodinated epirubicin ([125I]epirubicin) as targeting agents against MTHFD2-driven tumors. MTHFD2, which is pivotal in one-carbon metabolism, is notably upregulated in various cancers, presenting a novel target for radiopharmaceutical application. Through molecular docking and 200 ns molecular dynamics (MD) simulations, we assess the binding efficiency and stability of [125I]anastrozole and [125I]epirubicin with MTHFD2. Molecular docking illustrates that [125I]epirubicin has a superior binding free energy (∆Gbind) of −41.25 kJ/mol compared to −39.07 kJ/mol for [125I]anastrozole and −38.53 kJ/mol for the control ligand, suggesting that it has a higher affinity for MTHFD2. MD simulations reinforce this, showing stable binding, as evidenced by root mean square deviation (RMSD) values within a narrow range, underscoring the structural integrity of the enzyme–ligand complexes. The root mean square fluctuation (RMSF) analysis indicates consistent dynamic behavior of the MTHFD2 complex upon binding with [125I]anastrozole and [125I]epirubicin akin to the control. The radius of gyration (RG) measurements of 16.90 Å for MTHFD2-[125I]anastrozole and 16.84 Å for MTHFD2-[125I]epirubicin confirm minimal structural disruption upon binding. The hydrogen bond analysis reveals averages of two and three stable hydrogen bonds for [125I]anastrozole and [125I]epirubicin complexes, respectively, highlighting crucial stabilizing interactions. The MM-PBSA calculations further endorse the thermodynamic favorability of these interactions, with binding free energies of −48.49 ± 0.11 kJ/mol for [125I]anastrozole and −43.8 kJ/mol for MTHFD2-. The significant contribution of Van der Waals and electrostatic interactions to the binding affinities of [125I]anastrozole and [125I]epirubicin, respectively, underscores their potential efficacy for targeted tumor imaging and therapy. These computational findings lay the groundwork for the future experimental validation of [125I]anastrozole and [125I]epirubicin as MTHFD2 inhibitors, heralding a notable advancement in precision oncology tools. The data necessitate subsequent in vitro and in vivo assays to corroborate these results.

Synthesis and biological evaluation of orally active anti-Trypanosoma agents

In previous studies, we developed anti-trypanosome tubulin inhibitors with promising in vitro selectivity and activity against Human African Trypanosomiasis (HAT). However, for such agents, oral activity is crucial. This study focused on further optimizing these compounds to enhance their ligand efficiency, aiming to reduce bulkiness and hydrophobicity, which should improve solubility and, consequently, oral bioavailability. Using Trypanosoma brucei brucei cells as the parasite model and human normal kidney cells and mouse macrophage cells as the host model, we evaluated 30 new analogs synthesized through combinatorial chemistry. These analogs have fewer aromatic moieties and lower molecular weights than their predecessors. Several new analogs demonstrated IC50s in the low micromolar range, effectively inhibiting trypanosome cell growth without harming mammalian cells at the same concentration. We conducted a detailed structure–activity relationship (SAR) analysis and a docking study to assess the compounds’ binding affinity to trypanosome tubulin homolog. The results revealed a correlation between binding energy and anti-Trypanosoma activity. Importantly, compound 7 displayed significant oral activity, effectively inhibiting trypanosome cell proliferation in mice.

Circular dichroism spectrum of (R)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol in albumin: Alterations caused by complexation-Experimental and in silico investigation.

This study describes the interaction of human serum albumin (HSA) with the binol derivative (R)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol (R-BrB), which has its optical activity based on the prohibitive energetic barrier for conversion into the enantiomer (S)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol (S-BrB). The objective was to assess the ability of HSA to differentiate axial enantiomers based on their binding efficiency and their impact on the CD spectra. We discovered that both enantiomers were effective ligands, and the CD signal disappeared when equimolar amounts of R-BrB and S-BrB were simultaneously added, indicating no preference for either enantiomer. The complexation resulted in a significant signal increase at 250 nm and a bathochromic effect at 370 nm. Molecular docking simulations were performed, and the lower energy pose of R-BrB was selected for DFT calculations. The theoretical CD spectra of free and complexed R-BrB were obtained and showed alterations corroborating the experimental results. By comparing the difference spectrum (HSA:R-BrB minus HSA) with the spectrum of free RBrB in water or ethyl alcohol, we concluded that the CD signal intensification was due to the increased solubilization of R-BrB upon binding to HSA.

New mono and dinuclear half-sandwiched organoruthenium(II) complexes: Effect of dinuclearity on the biomolecular interaction and cytotoxicity

The present work describes the syntheses and structural characterization of new half sandwiched mono (complex 1) and dinuclear (complex 2) organoruthenium complexes derived from thiosemicarbazone ligand (L1). The molecular structures of compounds were characterized by analytical and multispectroscopic methods which corroborate well with single crystal XRD studies. DFT and TD-DFT studies of compounds revealed that HOMO electron density in L1 is localised on the thiosemicarbazide moiety while the LUMO electron density is evenly distributed over the ligand. However, in complex 1, the HOMO and LUMO is localised on the arene moiety and partially distributed over metal ion while HOMO and LUMO in complex 2 is equally delocalised throughout the complex. The collaborative preliminary DNA binding studies revealed that complexes 1 and 2 exhibited intercalative mode of interaction. The magnitude of DNA binding strength was determined by calculating Kb, K and Ksv values which demonstrated higher DNA binding propensity of complex 2. Furthermore, HSA binding studies of complexes also revealed better binding efficiency of dinuclear complex in contrast to mononuclear complex. The cytotoxic potential of dinuclear complex 2 was examined against triple negative breast cancer cell lines (MDA-MB-468 and MDA-MB-231) via MTT assay.

Methyl- versus ethyl-directed formation of square-planar Cobalt(II) and octahedral Cobalt(III) chelates of the in situ generated Schiff bases

Two mononuclear complexes [Co(LI)2] (1) and [Co(LII)3] (2) (HLI = N-cyclohexyl-3-methoxysalicylideneimine, HLII = N-cyclohexyl-3-ethoxysalicylideneimine) are reported. Although both compounds were obtained using the same synthetic procedure, 1 contains Co(II), while 2 is a Co(III) complex. The crystal structure of 1 was found to be the same as reported recently in the literature, while the crystal structure of 2 was established herein for the first time. The ligands in 1 are trans-1,5-N,O-coordinated, yielding a square planar CoN2O2 coordination core, while complex 2 adopts a meridinal isomeric form with both Δ and Λ configurations (Δ-mer-2 and Λ-mer-2). Optical properties of 1 and 2 were studied by the means of UV–vis spectroscopy in CH2Cl2 and MeOH. Both compounds absorb, mainly, in the UV region due to intraligand transitions and a ligand-to-metal charge transfer. The absorption spectra of both complexes also revealed two low intense bands at about 550 and 650 nm, which were attributed to d–d transitions. Molecular docking was applied to probe 1, Δ-mer-2 and Λ-mer-2 toward a series of the SARS-CoV-2 proteins. Both 1 and 2 are active against all the applied proteins; however, 1 is significantly more efficient with the docking scores being either comparable to or even higher of those of the initial ligands. The best binding affinity for 1 was established for PLpro, Mpro and Nsp3_range 207–379-MES. For both isomers of 2, the best binding scores were revealed with Nsp16_GTA site, PLpro, and Nsp3_range 207–379-MES (for Δ-mer-2) and Nsp16_SAM site (for Λ-mer-2). Ligand efficiency scores for the initial ligands as well as complexes 1 and 2 inside the binding sites of the applied proteins were also calculated. Of all complexes, the ligand efficiency scores for complexes of 1 with PLpro and Mpro are within the recommended ranges for a Hit, and the obtained ligand efficiency scores for complexes PLpro–1 and Mpro–1 are superior to those for the initial ligands.

Evaluation of Aflatoxin B1 Binding Capacity with Mix Toxin Binder using Central Composite Design

Aflatoxin B1 (afl B1) binding capacity of a mixed toxin binder used in poultry nutrition were determined using the central composite design technique. Experimental conditions such as pH, temperature and incubation time for the determination of the binding capacity of a mix binder were optimized for Central Composite Design. The impact of these three independent variables on the % binding of aflatoxin B1 was evaluated at different five levels (-1.68, -1, 0, 1, 1.68). The optimum experimental conditions were 5.8, 42°C, 94.11 min for pH, temperature and incubation time, respectively using quadratic model and desirability function. A significant effect of each independent variable was observed on the % binding efficiency of aflatoxin B1. In optimum experimental conditions, aflatoxin B1 binding capacity with mix toxin binder was found 97%. The results of the present study indicated that the mix binder is very suitable for binding of aflatoxin B1 and the central composite design can be used effectively in determining the optimized parameters for improving toxin binding capacity of aflatoxin B1.

Mycosporine-Like Amino Acids as a Potential Inhibitor of Tyrosinase-Related Protein 1: Computational Screening, Pharmacokinetics, and Molecular Dynamics Simulation.

Melanin is the major pigment responsible for the coloring of mammalian skin, hair, and eyes to defend against ultraviolet radiation. However, excessive melanin production has resulted in numerous types of hyperpigmentation disorders. Tyrosinase-related protein 1 (TYRP1) is a transmembrane glycoprotein enzyme found in many organisms, including humans, that plays an important role in melanogenesis. Thus, controlling the enzyme activity of TYRP1 with tyrosinase inhibitors is a vital step in the treatment of hyperpigmentation problems in humans. In the present investigation, virtual screening, pharmacokinetics, drug docking, and molecular dynamics (MD) simulation were used to find the most potent drug as an inhibitor of TYRP1 to effectively treat hyperpigmentation disorder. The 3D structure of TYRP1 was retrieved from the Protein Data Bank (PDB) database (PDB ID: 5M8M) and validated by the Ramachandran plot. Pharmacokinetics and drug-likeness showed that mycosporine 2 glycine (M2G) and shinorine (SHI) were the best compounds over other ligands in the same (P-1) structural pose. However, MD simulations of the M2G showed the highest CDOCKER interaction energy (-45.182kcal/mol) and binding affinity (-65.0529kcal/mol) as compared to SHI and reference drugs. The molecular binding modes RMSD and RMSF plots have exhibited more relevance to the M2G ligand in comparison to other drug ligands. The bioactivity and ligand efficiency profiles revealed that M2G is the most effective compound as a TYRP1 inhibitor. Thus, M2G could be used as a most effective drug for developing valuable sunscreen products to cure hyperpigmentation-related diseases.

Probing Ion-Receptor Interactions in Halide Complexes of Octamethyl Calix[4]Pyrrole.

Ion receptors are molecular hosts that bind ionic guests, often with great selectivity. The interplay of solvation and ion binding in anion host-guest complexes in solution governs the binding efficiency and selectivity of such ion receptors. To gain molecular-level insight into the intrinsic binding properties of octamethyl calix[4]pyrrole (omC4P) host molecules with halide guest ions, we performed cryogenic ion vibrational spectroscopy (CIVS) of omC4P in complexes with fluoride, chloride, and bromide ions. We interpret the spectra using density functional theory, describing the infrared spectra of these complexes with both harmonic and anharmonic second-order vibrational perturbation theory (VPT2) calculations. The NH stretching modes of the pyrrole moieties serve as sensitive probes of the ion binding properties, as their frequencies encode the ion-receptor interactions. While scaled harmonic spectra reproduce the experimental NH stretching modes of the chloride and bromide complexes in broad strokes, the high proton affinity of fluoride introduces strong anharmonic effects. As a result, the spectrum of F-·omC4P is not even qualitatively captured by harmonic calculations, but it is recovered very well by VPT2 calculations. In addition, the VPT2 calculations recover the intricate coupling of the NH stretching modes with overtones and combination bands of CH stretching and NH bending modes and with low-frequency vibrations of the omC4P macrocycle, which are apparent for all of the halide ion complexes investigated here. A comparison of the CIVS spectra with infrared spectra of solutions of the same ion-receptor complexes in d3-acetonitrile and d6-acetone shows how ion solvation changes the ion-receptor interactions for the different halide ions.

One-key based cryptographically generated address for location update in next generation IP mobility

Mobile devices have risen due to internet growth in recent years. The next generation of internet protocol is evolving for mobile devices to generate their addresses and get continuous services across networks to support the enormous number of addresses in network-based mobility. The mobile device updates its current location to its home network and the correspondent users through a binding update scheme in the visited network. Numerous studies have investigated binding update schemes to verify the reachability of the mobile device at its home network. However, most schemes endure security threats due to the incompetence of authenticating user identity and concealing the temporary location of mobile devices. To address these issues, this paper proposes a secure and efficient binding update scheme (One-CLU) by incorporating a one-key-based cryptographically generated address (CGA) to validate and conceal the address ownership of mobile devices with minimal computations. The security correctness of the proposed One-CLU scheme is verified using AVISPA – a model checker. Finally, the simulation and the numerical results showthat the proposed scheme significantly reduces communication payloads and costs for the binding update, binding refresh, and packet delivery.

Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits.

Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.

Small-Molecule Inhibitors of the m7G-RNA Writer METTL1.

We discovered the first inhibitors of the m7G-RNA writer METTL1 by high-throughput docking and an enzymatic assay based on luminescence. Eleven compounds, which belong to three different chemotypes, show inhibitory activity in the range 40-300 μM. Two adenine derivatives identified by docking have very favorable ligand efficiency of 0.34 and 0.31 kcal/mol per non-hydrogen atom, respectively. Molecular dynamics simulations provide evidence that the inhibitors compete with the binding of the cosubstrate S-adenosyl methionine to METTL1. We also present a soakable crystal form that was used to determine the structure of the complex of METTL1 with sinefungin at a resolution of 1.85 Å.

Assessment of fragment docking and scoring with the endothiapepsin model system.

Fragment-based screening has become indispensable in drug discovery. Yet, the weak binding affinities of these small molecules still represent a challenge for the reliable detection of fragment hits. The extent of this issue was illustrated in the literature for the aspartic protease endothiapepsin: When seven biochemical and biophysical in vitro screening methods were applied to screen a library of 361 fragments, very poor overlap was observed between the hit fragments identified by the individual approaches, resulting in high levels of false positive and/or false negative results depending on the mutually compared methods. Here, the reported in vitro findings are juxtaposed with the results from in silico docking and scoring approaches. The docking programs GOLD and Glide were considered with the scoring functions ASP, ChemScore, ChemPLP, GoldScore, DSXCSD, and GlideScore. First, the ranking power and scoring power were assessed for the named scoring functions. Second, the capability of reproducing the crystallized fragment binding modes was tested in a structure-based redocking approach. The redocking success notably depended on the ligand efficiency of the considered fragments. Third, a blinded virtual screening approach was employed to evaluate whether in silico screening can compete with in vitro methods in the enrichment of fragment databases.

Investigation of the Interaction of Monoamine Oxidase (MAO) Inhibitor Biscoumarins with Hemoglobin and Albumin Using Multi-Spectroscopic Techniques and Molecular Docking

Coumarin and their derivatives, such as biscoumarins, which are found as active ingredients in a variety of drugs, possess a wide range of biological activities. In this paper, the inhibitory effects of biscoumarin derivatives B1 and B2 on monoamine oxidase (MAO) enzyme activity were studied. Their binding mechanism to bovine serum hemoglobin (BHb) and bovine serum albumin (BSA) was investigated using molecular docking and multi-spectroscopic methods such as absorption, fluorescence, and synchronized fluorescence spectroscopy. The fluorescence quenching processes were analyzed using the Stern-Volmer, Lineweaver-Burk, and Hill methods. In this regard, Stern-Volmer quenching constants (Ksv), Lineweaver-Burk constants (KLB), and binding constants (Ka) were calculated at three temperatures (298, 310 and 322 K). The fluorescence studies showed that the binding of biscoumarins to BHb or BSA was a driven by static quenching. The Ka values of B2 to BHb and BSA (2179.11 and 18453.98 x 105 M-1) was larger than B1 at corresponding temperature (62.75 and 599.90 x105 M-1 for BHb and BSA, respectively), which indicates that the affinity of B2 toward the proteins were higher than that of B1. Moreover, thermodynamic parameters explained that hydrogen bonds were the main binding force stabilizing the protein-ligand complexes. Additionally, molecular docking studies have revealed binding energies, ligand efficiency values, and interactions with amino acid residues of proteins. The results of these investigations may be helpful in analyzing drug-protein binding of biscoumarins for potential future applications.

Alumina Ceramic Textiles as Novel Bacteria‐Capturing Wound Dressings

AbstractAlthough antimicrobial dressings have proven to be crucial in the treatment of wounds, they may give rise to antibiotic‐resistant strains or result in the release of endotoxins after bacterial death, which in turn inhibits wound healing. This study highlights the efficacy of a novel alumina ceramic textile as dressing that utilizes the principles of bacteria capture from the wound bed and inhibition of bacterial infiltration into the wound bed to reduce the bacterial burden and to inhibit the spread of infection, without the involvement of active antimicrobial substances or functional nanoparticles. The alumina textiles are compared to commercial dressings like the non‐woven mesh Cutimed Sorbact and gauzes from LEINA WERKE and performed significantly better in capturing bacteria. They are found to be effective against both Gram‐negative Escherichia coli and Gram‐positive Bacillus subtilis and show promising results in the presence of simulated wound fluid and in artificial wound bed tests from which they can be easily lifted without leaving behind any visible residues. In summary, the alumina textiles exhibit a highly efficient bacterial binding activity, possibly due to the intrinsic material properties of their hierarchical structure including the tricot knit mesh, small fiber diameters, pronounced fiber surface microtopography, and high specific surface area.

Influence the diphenhydramine hydrochloride–sodium carboxymethyl cellulose complex for nanoaggregate formation

This study aimed to create nanoaggregates that improve the synergistic interaction between the opposing charges in drug-polyelectrolyte complexes. In this study, sodium carboxymethyl cellulose (NaCMC) polyelectrolytes and diphenhydramine hydrochloride (DPC) drug molecules were used to form the nanoaggregate. The aggregation behaviour of NaCMC-DPC complexes was determined by using conductivity methods. The critical micelle concentrations (CMC) of NaCMC were reduced from 0.737 to 0.337 g/l in the aqueous and 29.18 mg/l in the DPC. The modified Corrin and Harkins (CH) and Frahm's approaches evaluated the binding efficiency of the NaCMC-DPC interaction. NaCMC-DPC complexes were examined by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques to conform to the formation of bilayer vesicles. Furthermore, we prepared the silver nanoparticles by using NaCMC-DPC complex mixtures. We demonstrated how NaCMC-DPC mixtures might influence the self-assembly of silver nanochain designs that differed from open "end-to-end" networks. The results indicated that the assembly of silver nanochains was regulated by a variation of electrostatic interactions inside the NaCMC-DPC components, which organized themselves around anisotropic nanochains surfaces. Among the optical properties altered by the linear assembly, the longitudinal surface plasmon resonance band at 624 nm has an enhanced redshift.

A Highly Efficient and Selective Glycine Based Schiff Base Fluorescent Probe for Dual Sensing of Zn(II) and Cu(II) and its Antibacterial Activity and BSA Interaction Studies

AbstractA mesogenic glycine based Schiff base compound of the type, (E)‐methyl 2‐((2‐hydroxy‐4‐(tetradecyloxy)benzylidene)amino)acetate (HL) has been successfully synthesized and characterized using analytical and spectroscopic techniques. The Schiff base compound was evaluated for chemosensor activity towards different metal ions using fluorescence spectroscopy. The experiment reveals highly efficient and selective “turn‐on” and “turn‐off” responses of the fluorescence intensity towards zinc(II) and copper(II), respectively, in presence of other metal ions. The binding constant and the stoichiometry ratio were determined using Benesi‐Hildebrand equation giving 1 : 1 stoichiometry. The limits of detection for both the metal ions were estimated from the fluorescence titration experiments. The reversibility nature of the Schiff base probe was also studied using EDTA as chelating ligand. The compound, HL exhibits two INHIBIT logic gates with chemical inputs (i) Zn2+ (IN1) and Cu2+ (IN2) and (ii) Zn2+ (IN1) and EDTA (IN2). An IMPLICATION logic gate was also obtained when Cu2+ (IN1) and EDTA (IN2) serve as chemical inputs. The compound was found to exhibit potent antibacterial activity and efficient binding interaction with BSA. Molecular docking studies were carried out in order to ascertain the degree of interaction and the nature of binding of the compound with the proteins.

Modification of hordein by gallic acid in ethanol-free environments: Impact of covalent and non-covalent interactions on structure, physicochemical properties and self-assembly

The objectives of this study were to modify hordein with gallic acid (GA) in alcohol-free media and to compare the impact of covalent and non-covalent binding on the properties of hordein. Covalent hordein-GA complexes (H-GA) and non-covalent hordein/GA complexes (H/GA) were distinguished by molecular weight, free sulfhydryl groups and free amino groups. Isothermal titration calorimetry (ITC) demonstrated that physical mixing induced non-covalent binding of GA to hordein via hydrogen bonding and hydrophobic interactions, with a lower binding efficiency than covalent ones. Both complexation types led to a structural shift of hordein toward disorder, while grafting of oligomeric GA and alkaline treatment resulted in lower surface hydrophobicity and higher antioxidant activity of H-GA compared to H/GA. The nanoparticles assembled from H-GA had smaller particle sizes and higher physical stability than those formed from H/GA. The results of this study may provide new insights into the modification of hordein by polyphenols.

Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics.

The global pandemic caused by the novel SARS-CoV-2 virus underscores the urgent need for therapeutic interventions. Targeting the virus's main protease (Mpro), crucial for viral replication, is a promising strategy. The current study aims to discover novel inhibitors of Mpro. The current study identified five natural compounds (myrrhanol B (C1), myrrhanone B (C2), catechin (C3), quercetin (C4), and feralolide (C5) with strong inhibitory potential against Mpro through virtual screening and computational methods, predicting their binding efficiencies and validated it using the in-vitro inhibition activity. The selected compound's toxicity was examined using the MTT assay on a human BJ cell line. Compound C1 exhibited the highest binding affinity, with a docking score of -9.82 kcal/mol and strong hydrogen bond interactions within Mpro's active site. A microscale molecular dynamics simulation confirmed the stability and tight fit of the compounds in the protein's active pocket, showing superior binding interactions. in vitro assays validated their inhibitory effects, with C1 having the most significant potency (IC50 = 2.85 μM). The non-toxic nature of these compounds in human BJ cell lines was also confirmed, advocating their safety profile. These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.