Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis. It forms a homodimer and binds to VEGF receptors to activate signaling pathways important for blood vessel growth and maintenance. In this study, we examined the structural and functional effects of two deleterious mutants, R262Q and C266Y, using integrative computational methods. Molecular dynamics simulations and principal component analysis showed that both mutations disrupted crucial interface interactions, including H-bonds, salt bridges, and disulfide linkages. As a result, the dimer conformation became less stable, which was also supported by binding free energy analysis. In addition, structural superimposition analysis revealed that both mutations changed the receptor-binding shape. This may block normal signaling and affect biological functions. Overall, our findings provide structural insights into how these mutations affect VEGFA dimer and may help guide the development of new therapeutics.

Deep eutectic solvents (DESs) are sustainable mixtures of hydrogen bond donors and acceptors that interact strongly to form liquids with melting points lower than their individual components. Various methods are employed to synthesize DESs; the most common one is the thermochemical approach which uses heat assisted with stirring to obtain the eutectic point of the DESs. However, this technique produces byproducts and/or impurities with side reactions or establishing covalent bonds between the molecules. In this study, the mechanochemical strategy is used to synthesize Type V DES which consists of non-ionic molecules. Some well-studied (type V) DES systems including menthol-octanoic acid, menthol-thymol, menthol-camphor, and thymol-camphor were selected for this study. A comprehensive suite of spectroscopic and thermoanalytical techniques, such as ATR-FTIR, PCA, 1NMR, DSC, and TGA were employed to elucidate the structural, compositional, and physicochemical characteristics of the eutectic mixtures synthesized via mechanochemical and conventional thermal approaches. The ATR-FTIR spectra confirmed DES formation through characteristic band shifts in the synthesized eutectic systems relative to those of the individual precursor components. The PCA of the FTIR spectra data demonstrated that both approaches yielded comparable outcomes for all the synthesized DESs. 1H NMR was used to understand chemical integrity. Moreover, TGA demonstrated the thermal robustness and decomposition behavior of the DES systems, while DSC confirmed eutectic formation and phase-transition characteristics through depressed melting events and altered thermal profiles. Additionally, the GC-MS analysis was used to detect byproducts or impurities of the studied eutectic mixtures. Physical measurements such as PH, Density were measured to understand the applicability of DES.

Heteroarenes containing boron-nitrogen (BN) bonds have attracted significant interest due to their often enhanced optoelectronic properties. The introduction of a nitro (-NO2) group into heteroarenes is particularly appealing because its strong electron-withdrawing character lowers the LUMO energy, reducing the HOMO-LUMO gap and inducing bathochromic shifts in both absorbance and emission spectra. However, NO2-substituted heteroarenes rarely fluoresce and typically suffer from aggregation-caused quenching (ACQ) of emission, limiting their practical applications. While strategies have been developed to counteract ACQ in NO2-functionalized systems, little attention has been directed toward NO2-substituted BN-heteroarenes, particularly three-coordinate boron species such as pyrrolidinone-fused-1,2-BN-heteroarenes (PBNHs). In this study, we address the ACQ issue in NO2-substituted 1,2-BN-heteroarenes by synthesizing four PBNHs, denoted as NO2-PBNHs 8, 9, 10, and 11, each featuring a -NO2 group at a distinct position (C8-C11) on the common scaffold. Using comprehensive photophysical analyses and time-dependent density functional theory (TD-DFT) calculations, we systematically evaluated how the -NO2 substituent's position influences photophysical properties and molecular packing. This work presents the first examples of electron-poor PBNHs with an identical framework exhibiting multifunctional, stimuli-responsive fluorescence properties. Modest positional changes of the -NO2 group produced unexpected behaviors. NO2-PBNHs 8 and 10 display both major aggregation-induced emission enhancement (AIEE) and solvatochromism within a single BN-aromatic backbone. NO2-PBNH 9, although prone to ACQ, exhibited positive solvatochromism, robust reversible thermochromism, and a unique pitched pi-stacking motif, highlighting its potential for temperature-sensing and charge-transport applications. NO2-PBNH 11 uniquely exhibited both minor ACQ and major AIE properties in one BN-aromatic backbone. Together, these findings demonstrate that regioselective nitration is an effective strategy to tune molecular packing and fluorescence behavior in BN-heteroarenes. Furthermore, cytotoxicity assays confirmed that NO2-PBNHs 8-11 are biocompatible, indicating potential for biological imaging. Overall, this study advances the understanding of aggregate formation in NO2-substituted PBNHs and provides design principles for next generation NO2-functionalized luminophores.

Deep Eutectic Solvents derived from amino acids are considered environmentally friendly because they are biodegradable, recyclable, and exhibit acceptable levels of toxicity. These solvents have various applications in various fields, such as biocatalysis, electrochemistry, extraction, and pharmaceuticals. Glutamine is an amino acid commonly found in human blood, and glycerol is a conventional solvent with rapid biodegradability. In this study, biodegradable amino acids based deep eutectic solvent (DES) was prepared from the mixture of glutamine and glycerol at a 1:3 (Glu: Gly) molar ratio, and differential scanning calorimetry (DSC) was used to confirm the phase transition. Exothermic and endothermic phase transitions detected at -5.12 °C and 2.83 °C respectively. Moreover, peak broadening due to spectral shifts of functional groups in the FTIR data confirmed the formation of DES, and PCA on the IR data concluded that the DES formation was glutamine-dominated. 1H NMR experiment was conducted to understand the chemical structure of the DES system. Molecular dynamics (MD) simulation and density functional theory were applied to study the structure and interaction of DES. The radial distribution function from the MD simulation confirmed the existence of three hydrogen bonds that stabilized the complex. Independent gradient model based on Hirshfeld partition (IGMH) analysis visualized the strongest interaction between the carboxylic acid of the glutamine and the alcoholic group of glycerol. Charge transfer analysis identified glycerol as a hydrogen bond donor and glutamine as a hydrogen bond acceptor. The application of our DES system was evaluated by measuring Density, pH and Conductivity. All these extensive insights will contribute to a deeper understanding of other biodegradable amino acid-based DESs and provide a broader approach to DES research.

The therapeutic deep eutectic solvent is a new class of deep eutectic solvent (DES), which includes at least an active pharmaceutical ingredient (API) as one of its components. Therapeutic DESs...

Bicyclic peptides have emerged as promising inhibitors due to their high binding affinity and selectivity for target receptors. While peptide inhibitors are highly target-specific and exhibit strong protein-binding capabilities, their potential is often limited by challenges such as proteolytic instability and flexible secondary structures, which can reduce their efficacy and bioavailability. This study focuses on designing and synthesizing bicyclic peptides and their molecular dynamics insights using scaffolds like 1,3,5-tris(bromomethyl)benzene (TBMB) and 1,3,5-triacryloylhexahydro-1,3,5-triazine (TATA) to enhance their stability and efficacy. The inhibitory activity of these peptides was assessed by targeting the main protease (Mpro), a key enzyme in viral replication of SARS-CoV-2. Mass spectrometry confirmed the purity of these peptides, and their inhibitory activity was evaluated using fluorescence resonance energy transfer (FRET) and selected ion monitoring (SIM)-based LC-MS assays. Computational modeling and molecular dynamics (MD) simulations revealed the structural basis of peptide-Mpro interactions, highlighting improved conformational stability and binding mechanisms. Bicyclic peptides demonstrated superior inhibition compared to linear analogs, with constraints significantly improving peptide stability and binding properties. Our findings highlight the potential of bicyclic peptides as a robust platform for developing next-generation therapeutics with enhanced pharmacokinetic and pharmacodynamic profiles.

Georgia produces half of the United States' peanuts, but the Southeast loses 25 million U.S. dollars annually due to aflatoxins from Aspergillus spp. contamination. Aspergillus flavus produces aflatoxin B1 (AFB1), one of the most toxic and carcinogenic substances affecting humans, livestock, and crops globally. Synthetic chemicals, genetic engineering, and biological control methods have been employed against A. flavus with limited success. Recently, there has been considerable interest in using plant-based antimicrobial compounds against mold. Our previous study established the aflatoxigenic properties of clove essential oil (EO) against A. flavus. We now evaluate the effectiveness of clove EO in artificially inoculated organic peanuts. Tween 20 served as a control, and all experiments were done in replicates. AFB1 was quantified using selected ion monitoring (SIM) based liquid chromatography-mass spectrometry (LC-MS) techniques. Our findings demonstrated that a high concentration of clove EO significantly reduced AFB1 in infected peanuts. Interestingly, a high reduction in AFB1 production was observed between 0 and 500 ppm, and the reduction increased slightly at higher concentrations of 1000 and 2000 ppm, respectively. Our results demonstrate that clove EO is most effective at reducing AFB1 in infected peanuts at low concentrations. We will further investigate the potential of clove EO as a biological control agent against A. flavus.

Alzheimer's disease affects over 10% of individuals above the age of 65, yet current treatments offer only limited and temporary relief. Acetylcholinesterase, a key enzyme in neurotransmitter breakdown, also contributes to disease progression by promoting β-amyloid aggregation. While previous studies have focused on the catalytic serine, a key proton transfer residue, His447 remains unexplored as a potential covalent binding site. In this study, we aim to interrupt the activation of Ser203 by covalently modifying His447, thereby shutting down the entire catalytic process. Here, we reported a computational pipeline to identify epoxide-based small molecules that covalently engage His447 and modulate AChE activity. From a curated library of >7,000 epoxides, three ligands (L5, L6, L7) were selected via covalent docking, molecular dynamics simulations, and drug-likeness profiling. Microsecond-scale simulations revealed stable binding across multiple subsites, with L5 exhibiting the most consistent RMSD and compact Rg values. Covalent engagement of L5 and L6 induced modest shifts in His447 (2.48 and 1.43 Å), whereas L7 maintained apo-like geometry. Furthermore, ADMET predictions indicated favorable profiles, with no cardiotoxicity risk. Our findings highlight His447 as a novel covalent target in AChE and support further in vivo investigation of the specificity and inhibitory mechanisms of these ligands.

Peptide-based inhibitors exhibit considerable potential as antiviral agents targeting SARS-CoV-2. In this study, we designed analogs (TLP-1, TLP-2, and TLP-3) of Temporin L (TL) peptide with the specific objective of selectively interacting with and targeting the main protease (Mpro) of SARS-CoV-2. The synthesis and characterization of TLPs were employed using solid-phase peptide synthesis and LC-MS respectively. CD and solution NMR spectroscopy elucidated the overall structure of the TLPs relative to TL, revealing folded peptides where introduced mutations alter the peptide conformation for binding to Mpro. MD simulations highlighted improvements in TLP's stability and interactions with Mpro. FRET based protease activity assays provided evidence that TLPs exhibited enhanced inhibitory activity against Mpro. The results of our study reveal the promising prospects of TLPs as attractive candidates for in vivo investigations, thereby contributing to the progress of peptide-based therapeutic approaches targeting SARS-CoV-2.

Recent developments in mechanochemistry have enabled the preparation of deep eutectic solvents (DESs) that can be a greener and viable alternative to the traditional thermal DESs. Since the mechanochemical method can be performed under ambient conditions, the mechanical energy generated during the grinding process can be sufficient to dissolve the solid HBA and HBD components and create a homogeneous mixture of DES. As thermally prepared DESs involve heating their components, often an extended duration of heating may alter their functionality through byproduct or covalent bond formation. In contrast, the mechanochemical preparation of DES requires no heating. This significantly reduces energy consumption and reduces the chance of the formation of any covalent bonds. In this study, we prepared three classes of DES using thermal and mechano-assisted rotary tumbler ball milling techniques without the application of any heat and analyzed them using multitechnique approaches, including physical, spectroscopic, statistical, and thermal analysis. Spectroscopic FT-IR and 1H NMR investigations were used to confirm the formation of DESs and to detect the presence of any impurities or byproducts in both methods. Principal component analysis (PCA) of the FTIR spectra data showed that both methods produced similar results for all of the DESs prepared. Thermal analysis of the DESs was performed by using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The physical properties of DES were measured for all three types of DESs. The results revealed that in all cases, even and almost for more challenging DESs, the mechanochemical-assisted rotary tumbler ball milling method showed unique advantages in comparison with traditional preparation processes, in terms of energy, performance, security, functionality, operating time, economics, and thus industrial-scale reality. This method can reveal the pathway to meet the industry's new expectations for DES production and the future development of this green solvent-based process in different fields.

Photolabile protecting groups (PPGs) that enable real-time monitoring of uncaging processes are highly sought after for tracking product release during and after photolysis. Few PPGs facilitate direct detection of uncaging events through a fluorescence signal, with o-nitrobenzyl (o-NB) PPG derivatives being the only known examples exhibiting pro-fluorescent properties. In this study, we broaden the scope of accessible pro-fluorescent o-NB PPGs for direct monitoring of product release by reporting two new pro-fluorescent, ethynylthiophene-based, and visible light-absorbing o-NB PPGs, referred to as NPETs 1 and 2. UV-Vis spectroscopy confirmed the complete cleavage of hydroxamic acid (HA) derivatives from NPETs 1 and 2, as evidenced by a blue shift and reduced absorbance intensity. This step likely proceeds through an aci-nitro intermediate, supported by both spectroscopic and computational examinations. We also assessed the released HA products by monitoring the corresponding increase in fluorescence intensity, which corresponds to the co-generated nitrosoketone by-product. The 4-fold and 3-fold increase in fluorescent intensity for NPETs 1 and 2, respectively, was easily observable with the naked eye. Time-course 1H NMR experiments revealed that NPET 2 exhibits greater stability than NPET 1, showing only minor degradation after 30 days at ambient conditions. (TD)-DFT calculations revealed that the nitrosoketone by-product emission occurs from the S2 singlet excited state, violating Kasha's rule. This study highlights the efficacy of pro-fluorescent, ethynylthiophene-based o-NB PPGs in facilitating precise photoreactions under mild acidic conditions. Their pro-fluorescence response and minimal degradation under ambient conditions indicate their potential for application in releasing synthetically difficult-to-synthesize functional groups.

HIV-1 integrase (IN), a major protein in the HIV life cycle responsible for integrating viral cDNA into the host DNA, represents a promising drug target. Small peptides have emerged as antiviral therapeutics for HIV because of their facile synthesis, highly selective nature, and fewer side effects. However, selecting the best candidates from a vast pool of peptides is a daunting task. In this study, multistep virtual screening was employed to identify potential peptides from a list of 280 HIV inhibitory peptides. Initially, 80 peptides were selected based on their minimum inhibitory concentrations (MIC). Then, molecular docking was performed to evaluate their binding scores compared to HIP000 and HIP00N which are experimentally validated HIV-1 integrase binding peptides that were used as a positive and negative control, respectively. The top-scoring docked complexes, namely, IN-HIP1113, IN-HIP1140, IN-HIP1142, IN-HIP678, IN-HIP776, and IN-HIP777, were subjected to initial 500 ns molecular dynamics (MD) simulations. Subsequently, HIP776, HIP777, and HIP1142 were selected for an in-depth mechanistic study of peptide interactions, with multiple simulations conducted for each complex spanning one microsecond. Independent simulations of the peptides, along with comparisons to the bound state, were performed to elucidate the conformational dynamics of the peptides. These peptides exhibit strong interactions with specific residues, as revealed by snapshot interaction analysis. Notably, LYS159, LYS156, VAL150, and GLU69 residues are prominently involved in these interactions. Additionally, residue-based binding free energy (BFE) calculations highlight the significance of HIS67, GLN148, GLN146, and SER147 residues within the binding pocket. Furthermore, the structure-activity relationship (SAR) analysis demonstrated that aromatic amino acids and the overall volume of peptides are the two major contributors to the docking scores. The best peptides will be validated experimentally by incorporating SAR properties, aiming to develop them as therapeutic agents and structural models for future peptide-based HIV-1 drug design, addressing the urgent need for effective HIV treatments.

Addressing the acute pesticide poisoning and toxicity to humans, is a global challenge of top priority. Serum albumin is the most abundant plasma protein, capable of binding with herbicide and pesticide residues. This study reports multifaceted approaches for in-depth and robust investigation of the molecular interactions of selected pesticides, including propanil (PPL), bromoxynil (BXL), metolachlor (MLR) and glyphosate (GPE) with bovine serum albumin (BSA) proteins using experimental (Raman and FTIR spectroscopy, native mass spectrometry and high field 1H NMR), molecular dynamics (MD) simulation and principal component analysis (PCA). The binding of pesticides with BSA resulted in BSA amide I and amide II Raman spectral shifts. PCA of Raman spectra of serum-pesticide complexes showed the grouping of pesticides on the score plot based on the similarities and differences in pesticides' chemical structures. Native mass spectrometry results revealed strong adduct formation of the pesticides with the protein. The observed changes in chemical shifts, peak broadening or peak disappearance of characteristic proton signals of the pesticides, indicated altered chemical environments due to binding BSA-pesticides interactions. The results of MD simulation conducted for over 500 ns revealed strong pesticides interaction with LEU197, LEU218, LEU237, TRP213, SER286 and ILE289 residues to the site I of BSA. Free energy landscapes provided insights into the conformational changes in BSA on the binding of pesticides. Overall, the experimental and computational results are in consonant and indicate the binding of pesticides into the site I and site II (sub-domain IIA) of the BSA via hydrogen bonding, non-covalent and hydrophobic interactions.Communicated by Ramaswamy H. Sarma

The mode of interaction of surfactant with drug remains a keen interest in the research area owing to the improvement of drug carrier systems in therapeutic formulations. In order to investigate the drug-surfactant interactions between triton X-100 (TTX-100) and an antidiabetic drug metformin hydrochloride (MMH); the phase partitioning behavior (in aq. Na2SO4, Na3PO4, and sodium dodecyl sulfate (SDS)), micellization, as well as the molecular dynamics simulation of the TTX-100 and MMH drug mixture have been examined. The cloud point (CP) values of TTX-100 + MMH system have been detected to be lessened with the growing concentration of Na2SO4 and Na3PO4, where the CP values follow the order: CP (aq. Na3PO4) < CP (aq. Na2SO4). The introduction of SDS caused the enhancement of CP for the study system. The critical micelle concentration (CMC) for the TTX-100 + MMH mixture was determined using the absorbance vs. log [TTX-100] plot using the UV-Visible spectroscopic tool. The CMC values were attained to be heightened with the rising content of MMH and, thus, the presence of MMH disfavors the micelle growth of TTX-100. The free energy changes of clouding (Delta H-c(0)) and micellization (Delta S-c(0)) have been noticed as positive (nonspontaneous process) and negative (spontaneous process), respectively. The changes in standard enthalpy (Delta H-c(0)), entropy (Delta S-c(0)), thermodynamic transfer parameters (Delta G(c,tr)(0), Delta H-c,tr(0), Delta S-c,tr(0)), and the Delta H-c(0)-Delta S-c(0) compensation factors were also computed and appropriately explained. The values of Delta H-c(0) and Delta S-c(0) recommend that the clouding of TTX-100 + MMH in aq. Na2SO4 and Na3PO4 is controlled by the enthalpy alone, while the process is controlled by the entropy in aq. SDS solution. In this process, the electrostatic interactions and hydrophobic force are recommended as core forces among the employed media. By applying the molecular dynamics simulation, the atomic-scale interactions between MMH and TTX-100 were unveiled, showing a strong correlation with the experimental outcomes.

This investigation evaluated the therapeutic benefit of apocynin in isoproterenol (ISO)-induced cardiac damage in rats. ISO-administered male Wistar rats were treated with apocynin for 2 weeks. Blood plasma and left ventricle of heart tissues were collected and analyzed for oxidative stress-related parameters such as malondialdehyde (MDA), advanced oxidation protein product (AOPP), and nitric oxide (NO). The activities of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase were also measured. The gene expressions of oxidative stress-related proteins such as Nrf-2, HO-1, and HO-2 in cardiac tissues were also measured. In silico studies like molecular docking and molecular dynamics were also performed to detect how apocynin interacts with NADPH and nitric oxide synthase at the molecular level. This investigation revealed significant elevation of serum transferase enzymes and creatinine kinase-Muscle Brain (CK-MB) activities in ISO-administered rats compared to the control. Apocynin effectively normalized the serum transferases and CK-MB activities in the blood of ISO-stressed rats. Moreover, ISO-induced elevations of MDA, NO, and AOPP levels were also suppressed by apocynin treatment. Consistently, apocynin restored the reduced SOD and catalase activities in ISO-administered rats. This restoration of enzyme activity might be due to the increased expression of Nrf-2 and HO-1 and reduced expression of iNOS and TNF-α in ISO-administered rats. Histological analysis revealed that apocynin treatment ameliorated the mononuclear cell adherence and fibrosis in the cardiac tissue of ISO-administered rats. Computational studies also support the experimental findings. This study demonstrates that apocynin prevents ISO-induced cardiac injury not only by preventing inflammation but also by empowering the antioxidant defense system.

One of the most popular topics in sustainable chemistry is the creation of new eco-friendly solvents. Deep eutectic solvents (DESs) have been established as accessible and affordable substitutes for ionic liquids. Herein, we studied the formation of a novel amino acid-based DES (AADES) considering l-threonine as a hydrogen bond acceptor and glycerol as a hydrogen bond donor. Owing to their complexity, a comprehensive understanding of DESs requires combined efforts that integrate experimental observations with computational approaches. The validation of the synthesized DES was initially performed through FTIR spectroscopy, where significant changes in bond-bending vibrations indicated strong non-covalent bond formation. In differential scanning calorimetry (DSC) analysis, the 1 : 3 Thr/Gly deep eutectic system displayed phase transitions marked by a pronounced peak at -22 degrees C, which was lower than the melting points of threonine (Thr) and glycerol (Gly). H-1-NMR studies also revealed hydrogen bonding intermolecular interactions between glycerol and threonine. Deshielded chemical shifts of proton signals of both glycerol and threonine are due to the local changes in electron density induced by the closeness of electronegative oxygens via the inductive effect, which supports the formation of the conformer (3 : 1 glycerol/threonine DES). Molecular dynamics (MD) simulation was employed to acquire a comprehensive understanding of how these solvents form and function at both the molecular and macroscopic levels. RDF and CDF analyses revealed the non-bonding sites (C-O & ctdot;H and C=O & ctdot;H), interaction intensity (2-4.7 & Aring;), and predominant angles (135-180 and 0-30 degrees) governing the process by which hydrogen bonds originate in the DES. SDF uncovered the conformations of the liquid DES and highlighted its variability, particularly in terms of clusters. The bulk properties of DESs are of paramount significance because they are intricately linked to their diverse applications. Transport property values were obtained through specialized MD simulations, providing crucial insights into the behavior of the systems. Non-equilibrium molecular dynamics (NEMD) simulations were performed to assess the rheological properties of viscosity at three distinct temperatures (298 K, 313 K, and 328 K). The obtained viscosity, surface tension, and self-diffusion coefficient values appear practical and fall within a reasonable range when compared to those of other well-known DESs.

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in viral replication and transcription and received great attention as a vital target for drug/peptide development. Therapeutic agents such as small-molecule drugs or peptides that interact with the Cys-His present in the catalytic site of Mpro are an efficient way to inhibit the protease. Although several emergency-approved vaccines showed good efficacy and drastically dropped the infection rate, evolving variants are still infecting and killing millions of people globally. While a small-molecule drug (Paxlovid) received emergency approval, small-molecule drugs have low target specificity and higher toxicity. Besides small-molecule drugs, peptide therapeutics are thus gaining increasing popularity as they are easy to synthesize and highly selective and have limited side effects. In this study, we investigated the therapeutic value of 67 peptides targeting Mpro using molecular docking. Subsequently, molecular dynamics (MD) simulations were implemented on eight protein-peptide complexes to obtain molecular-level information on the interaction between these peptides and the Mpro active site, which revealed that temporin L, indolicidin, and lymphocytic choriomeningitis virus (LCMV) GP1 are the best candidates in terms of stability, interaction, and structural compactness. These peptides were synthesized using the solid-phase peptide synthesis protocol, purified by reversed-phase high-performance liquid chromatography (RP-HPLC), and authenticated by mass spectrometry (MS). The in vitro fluorometric Mpro activity assay was used to validate the computational results, where temporin L and indolicidin were observed to be very active against SARS-CoV-2 Mpro with IC50 values of 38.80 and 87.23 μM, respectively. A liquid chromatography-MS (LC-MS) assay was developed, and the IC50 value of temporin L was measured at 23.8 μM. The solution-state nuclear magnetic resonance (NMR) structure of temporin L was determined in the absence of sodium dodecyl sulfate (SDS) micelles and was compared to previous temporin structures. This combined investigation provides critical insights and assists us to further develop peptide inhibitors of SARS-CoV-2 Mpro through structural guided investigation.

Deep eutectic solvents (DESs) have emerged as potential alternatives to traditional solvents, offering unique properties and potential applications. However, the excessively viscous nature of DESs limits their applications in extraction, separation, electrodeposition, battery and energy storage, and drug delivery. The presence of water as a cosolvent can substantially reduce the viscosity and density of DESs and open widespread applications. The aim of this research is to elucidate the nanostructures of DESs in the presence of water, which is key to understanding and tuning their properties for various applications. Multitechnique approaches such as Raman spectroscopy, differential scanning calorimetry (DSC), 1H nuclear magnetic resonance, and an all-atom molecular dynamics (MD) simulation were employed to determine how water affects the molecular-level arrangement, dynamics, and interactions of a L-menthol/acetic acid (AA)-based hydrophobic DES at various hydration levels. A pure DES exhibits significant H-bonding interactions with menthol and AA. As water is added, these interactions weaken, new H-bonding interactions between the DES system and water emerge, and the DES turns into a binary mixture as evident from visual inspection and DSC and Raman experiments. As the contacts between menthol and AA weaken and the number of contacts between water molecules increases, about 50%-60% of water leads to a different system. Additionally, principal component analysis assists us in identifying the sequences in which the characteristics of the DES change with the gradual addition of water. The changes detected in the nanostructural characteristics of the L-menthol/AA DES can aid to develop a less viscous and dense DES suited for special applications. The combined Raman spectroscopic and MD simulation analysis provided deep molecular-level insights into the structural and dynamic changes occurring in the Men-AA system with varying water content. The findings obtained from this research not only enhance our comprehension of the influence of water on altering the characteristics of DES but also facilitate the development of DES systems specifically designed for industrial operations that need reduced viscosity and density.

Dengue fever has emerged as a critical health threat in Bangladesh and recorded the highest mortality rate in 2023. It is also a global concern, impacting 390 million people annually. No FDA-approved drug is available yet to treat dengue. The Structure-activity relationship (SAR) can be a significant approach for predicting novel inhibitors and repurposing existing drugs against dengue. This study aims to develop a machine-learning model that can predict the pIC50 (M) value of novel inhibitors against the dengue NS2B-NS3 protein. In this connection, this methodology uses a structure-activity dataset of 1141 compounds. Each compound contains 1544 molecular descriptors (ID and 2D) considered as structural features and their effective percentage inhibition concentration at 50% (pIC50), against 'DENV-2 NS2B-NS3‘. This research implements 9 tree-based, and 9 other distinct machine learning algorithms considering all features to identify the best-performing algorithm. In the baseline test, the tree-based algorithms outperform the other conventional algorithms where the Extra Trees algorithm performs the best among the tree-based algorithms. Furthermore, the study utilizes the Random Forest algorithm to extract individual features' importance against pIC50. The features are fed into 6 different tree-based algorithms in the chronology of feature importance. The experiments depict an impressive result that some of the features have a negative impact on prediction. Eventually, the work eliminates 1502 molecular descriptors to differentiate only 42 important features that can produce the lowest RMSE of 0.3035, MSE of 0.0924 MAPE of 0.0515, and MAE of 0.2309. This optimized model has outperformed the baseline model evidently.