Structure-activity Relationship Research Articles

Exploring Nanozymes for Organic Substrates: Building Nano-organelles.

Since the discovery of the first peroxidase nanozyme (Fe3O4), numerous nanomaterials have been reported to exhibit intrinsic enzyme-like activity toward inorganic oxygen species, such as H2O2, oxygen, and O2•-. However, the exploration of nanozymes targeting organic compounds holds transformative potential in the realm of industrial synthesis. This review provides a comprehensive overview of the diverse types of nanozymes that catalyze reactions involvingorganic substrates and discusses their catalytic mechanisms, structure-activity relationships, and methodological paradigms for discovering new nanozymes. Additionally, we propose a forward-looking perspective on designing nanozyme formulations to mimic subcellular organelles, such as chloroplasts, termed "nano-organelles". Finally, we analyze the challenges encountered in nanozyme synthesis, characterization, nano-organelle construction and applications while suggesting directions to overcome these obstacles and enhance nanozyme research in the future. Through this review, our goal is to inspire further research efforts and catalyze advancements in the field of nanozymes, fostering new insights and opportunities in chemical synthesis.

DIGEP-Pred 2.0: A web application for predicting drug-induced cell signaling and gene expression changes.

The analysis of drug-induced gene expression profiles (DIGEP) is widely used to estimate the potential therapeutic and adverse drug effects as well as the molecular mechanisms of drug action. However, the corresponding experimental data is absent for many existing drugs and drug-like compounds. To solve this problem, we created the DIGEP-Pred 2.0 web application, which allows predicting DIGEP and potential drug targets by structural formula of drug-like compounds. It is based on the combined use of structure-activity relationships (SARs) and network analysis. SAR models were created using PASS (Prediction of Activity Spectra for Substances) technology for data from the Comparative Toxicogenomics Database (CTD), the Connectivity Map (CMap) for the prediction of DIGEP, and PubChem and ChEMBL for the prediction of molecular mechanisms of action (MoA). Using only the structural formula of a compound, the user can obtain information on potential gene expression changes in several cell lines and drug targets, which are potential master regulators responsible for the observed DIGEP. The mean accuracy of prediction calculated by leave-one-out cross validation was 86.5 % for 13377 genes and 94.8 % for 2932 proteins (CTD data), and it was 97.9 % for 2170 MoAs. SAR models (mean accuracy-87.5 %) were also created for CMap data given on MCF7, PC3, and HL60 cell lines with different threshold values for the logarithm of fold changes: 0.5, 0.7, 1, 1.5, and 2. Additionally, the data on pathways (KEGG, Reactome), biological processes of Gene Ontology, and diseases (DisGeNet) enriched by the predicted genes, together with the estimation of target-master regulators based on OmniPath data, is also provided. DIGEP-Pred 2.0 web application is freely available at https://www.way2drug.com/digep-pred.

Pyrene‐Alkyne‐Based Conjugated Porous Polymers with Skeleton Distortion‐Mediated ⋅O2− and 1O2 Generation for High‐Selectivity Organic Photosynthesis

AbstractReactive oxygen species (ROS) play a crucial role in determining photocatalytic reaction pathways, intermediate species, and product selectivity. However, research on ROS regulation in polymer photocatalysts is still in its early stages. Herein, we successfully achieved series of modulations to the skeleton of Pyrene‐alkyne‐based (Tetraethynylpyrene (TEPY)) conjugated porous polymers (CPPs) by altering the linkers (1,4‐dibromobenzene (BE), 4,4′‐dibromobiphenyl (IP), and 3,3′‐dibromobiphenyl (BP)). Experiments combined with theoretical calculations indicate that BE‐TEPY exhibits a planar structure with minimal exciton binding energy, which favors exciton dissociation followed by charge transfer with adsorbed O2 to produce ⋅O2−. Thus BE‐TEPY shows optimal photocatalytic activity for phenylboronic acid oxidation and [3+2] cycloaddition. Conversely, the skeleton of BP‐TEPY is significantly distorted. Its planar conjugation decreases, intersystem crossing (ISC) efficiency increases, which makes it more prone for resonance energy transfer to generate 1O2. Therefore, BP‐TEPY displays best photocatalytic activity in [4+2] cycloaddition and thioanisole oxidation. Both above reactant conversion and its product selectivity exceed 99 %. This work systematically reveals the intrinsic structure–activity relationship among the skeleton structure of CPPs, excitonic behavior, and selective generation of ROS, providing new insights for the rational design of highly efficient and selective CPPs photocatalysts.

Navigating pharmacophore space to identify activity discontinuities: a case study with BCR-ABL.

The exploration of chemical space is a fundamental aspect of chemoinformatics, particularly when one explores a large compound data set to relate chemical structures with molecular properties. In this study, we extend our previous work on chemical space visualization at the pharmacophoric level. Instead of using conventional binary classification of affinity (active vs inactive), we introduce a refined approach that categorizes compounds into four distinct classes based on their activity levels: super active, very active, active, and inactive. This classification enriches the color scheme applied to pharmacophore space, where the color representation of a pharmacophore hypothesis is driven by the associated compounds. Using the BCR-ABL tyrosine kinase as a case study, we identified intriguing regions corresponding to pharmacophore activity discontinuities, providing valuable insights for structure-activity relationships analysis.

Fast and facile synthesis of amidine-incorporated degradable lipids for versatile mRNA delivery in vivo.

Lipid nanoparticles (LNPs) are widely used for mRNA delivery, with cationic lipids greatly affecting biodistribution, cellular uptake, endosomal escape and transfection efficiency. However, the laborious synthesis of cationic lipids limits the discovery of efficacious candidates and slows down scale-up manufacturing. Here we develop a one-pot, tandem multi-component reaction based on the rationally designed amine-thiol-acrylate conjugation, which enables fast (1 h) and facile room-temperature synthesis of amidine-incorporated degradable (AID) lipids. Structure-activity relationship analysis of a combinatorial library of 100 chemically diverse AID-lipids leads to the identification of a tail-like amine-ring-alkyl aniline that generally affords efficacious lipids. Experimental and theoretical studies show that the embedded bulky benzene ring can enhance endosomal escape and mRNA delivery by enabling the lipid to adopt a more conical shape. The lead AID-lipid can not only mediate local delivery of mRNA vaccines and systemic delivery of mRNA therapeutics, but can also alter the tropism of liver-tropic LNPs to selectively deliver gene editors to the lung and mRNA vaccines to the spleen.

Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity.

Tropane-containing small molecules like scopolamine are a promising class of psychoplastogens. However, their potent antagonism of all muscarinic receptor subtypes presents the potential for undesirable anticholinergic side effects. In an effort to decouple their neuroplasticity-promoting effects from their muscarinic activity, we performed phenotypic structure-activity relationship studies across a variety of structurally distinct subclasses of tropanes. We discovered several novel tropanes capable of significantly increasing cortical neuronal growth while exhibiting drastically reduced activity at all muscarinic receptor subtypes compared to scopolamine.

The Sources, Structures and Cytotoxicity of Animal-derived Bisindole Compounds.

Bisindole compounds constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the past four decades, researchers have isolated 229 animal-derived bisindole compounds (ADBCs) from various animals. These compounds demonstrate a wide range of pharmacological properties, including cytotoxicity, antibacterial, antifungal, antiviral, and other activities. Notably, among these activities, cytotoxicity emerges as the most prominent characteristic of ADBCs. This review also summarizes the structureactivity relationship (SAR) studies associated with the cytotoxicity of these compounds and explores the druggability of these compounds. In summary, our objective is to provide an overview of the research progress concerning ADBCs, with the aim of fostering their continued development and utilization.

Screening Potential Nitrification Inhibitors through a Structure–Activity Relationship Study—The Case of Cinnamic Acid Derivatives

Using a nitrification inhibitor to decrease nitrification rates in soil represents a promising strategy to improve nitrogen fertilizer use efficiency. Nonetheless, rapid screening of nitrification inhibitors remains challenging. In this study, we propose a strategy to screen potential nitrification inhibitors through a structure–activity relationship (SAR) study based on a rapid determination of nitrification inhibition. To demonstrate this, the nitrification inhibition potentials of cinnamic acid derivatives against Nitrosomonas europaea growth were evaluated in a liquid culture. The SAR study showed that hydroxyl and fluoride groups were the favorable substituents on the benzene ring, and the ester group and double bond in the side chain were essential for maintaining high inhibition efficacy. Three compounds with notable inhibitory efficacy (EC50 = 8–25 μM) were further assessed in agricultural soil, and they displayed a noteworthy reduction in nitrification rate and bacterial amoA gene numbers. Based on the results, we identified methyl cinnamate, methyl 4-hydroxycinnamate, and methyl 4-fluorocinnamate as promising candidates for nitrification inhibition.

Fingerprint profiling for quality evaluation and the related biological activity analysis of polysaccharides from Liuweizhiji Gegen-Sangshen beverage

IntroductionLiuweizhiji Gegen-Sangshen beverage (LGS) is popular in China, which has been used for alleviating alcohol-mediated discomfort and preventing alcoholic liver disease (ALD). This beverage is consisted of six herbal components that are known as functional foods and fruits. LGS is rich in polysaccharides, however, the activity and quality evaluation of LGS-derived polysaccharides remain unexplored. The purpose of this study is thus to establish a comprehensive quality control methodology for the assessment of LGS polysaccharides (LGSP) and to further explore the anti-oxidant, anti-inflammatory as well as prebiotic effect of LGSP.MethodsLGSP was extracted, followed by analysis of molecular weight distribution, monosaccharide content and structural characterization via integrating the application of high-performance size exclusion chromatography (HPSEC), 1-phenyl-3-methyl-5-pyrazolone-HPLC (PMP-HPLC), fourier transform infrared spectroscopy (FT-IR) as well as nuclear magnetic resonance spectroscopy (NMR) techniques. The anti-oxidation activity of LGSP was determined by DPPH, ABTS, hydroxyl radical scavenging capacity and total antioxidant capacity. The anti-inflammation of LGSP were assessed on the RAW 264.7 cells. The effect of LGSP on growth of Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis was evaluated.ResultsThe results demonstrated that LGSP had two molecular weight distribution peaks, with the average molecular weights of (6.569 ± 0.12) × 104 Da and (4.641 ± 0.30) × 104 Da. LGSP was composed of 8 monosaccharides, with galacturonic acid, glucose rhamnose and galactose representing the highest molar ratios. Homogalacturonic acid (HG) type and rhamnosegalacturonic acid glycans I (RG-I) type and α-1,4-glucan were present in LGSP. LGSP concentration in LGS was 17.94 ± 0.28 mg/mL. Furthermore, fingerprint analysis combined with composition quantification of 10 batches of LGSP demonstrated that there was a high similarity among batches. Notably, LGSP exhibited anti-oxidant effect and inhibited expressions of pro-inflammatory factors (TNF-α and IL-6) in LPS-stimulated RAW 264.7 cells. In addition, LGSP remarkably promoted the proliferation of probiotics Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis, showing good prebiotic activity.DiscussionThe results of present study would be of help to gain the understanding of structure–activity relationship of LGSP, provide a reference for quality evaluation of bioactive LGSP, and facilitate development of unique health and functional products in the future.

Covalent isothiocyanate inhibitors of macrophage migration inhibitory factor as potential colorectal cancer treatments.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with roles in innate and adaptive human immune responses, as well as inflammation. MIF exerts its biological activity by binding to the cell surface receptor CD74 as well as intracellular signalling proteins. MIF also possesses keto-enol tautomerase activity. Inhibition of the tautomerase activity has been associated with loss of biological activity of MIF and a potential anticancer target. Isothiocyanates (ITCs) are a class of compounds present in cruciferous vegetables that inhibit the MIF tautomerase activity via covalent modification of the N-terminal proline. A range of substituted ITCs featuring benzyl, phenethyl and phenyl propyl isothiocyanates were designed, synthesised and tested to determine any structure activity relationship for inhibiting MIF. Crystal structures of covalent compounds 8 and 9 in complex with rhMIF revealed key hydrogen bonding and edge-to-face π stacking interactions. Compound 9 and 11 with sub micromolar activity were tested in the NCI60 cancer cell lines panel. Both compounds showed tissue-specific reduced growth in colon and renal cancer cell lines, while one of these showed potent, dose-dependent inhibition of growth against all seven colon cancer cell lines (GI50 < 2.5 µM) and all eight renal cancer cell lines (GI50 < 2.2 µM).

Assessing the Effects of Thiazole-Carboxamide Derivatives on the Biophysical Properties of AMPA Receptor Complexes as a Potential Neuroprotective Agent

An optimal balance between excitatory and inhibitory transmission in the central nervous system provides essential neurotransmission for good functioning of the neurons. In the neurology field, a disturbed balance can lead to neurological diseases like epilepsy, Alzheimer’s, and Autism. One of the critical agents mediating excitatory neurotransmission is α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, which are concerned with synaptic plasticity, memory, and learning. An imbalance in neurotransmission finally results in excitotoxicity and neurological pathologies that should be corrected through specific compounds. Hence, the current study will prove to be an evaluation of new thiazole-carboxamide derivatives concerning AMPAR-modulating activity and extended medicinal potential. In the current project, five previously synthesized thiazole-carboxamide derivatives, i.e., TC-1 to TC-5, were used to interact with the AMPARs expressed in HEK293T cells, which overexpress different subunits of the AMPAR. Patch-clamp analysis was carried out while the effect of the drugs on AMPAR-mediated currents was followed with a particular emphasis on the kinetics of inhibition, desensitization, and deactivation. All tested TC compounds, at all subunits, showed potent inhibition of AMPAR-mediated currents, with TC-2 being the most powerful for all subunits. These compounds shifted the receptor kinetics efficiently, mainly enhancing the deactivation rates, and hence acted as a surrogate for their neuroprotective potentials. Additionally, recently published structure–activity relationship studies identified particular substituent groups as necessary for improving the pharmacologic profiles of these compounds. In this regard, thiazole-carboxamide derivatives, particularly those classified as TC-2, have become essential negative allosteric modulators of AMPAR function and potential therapeutics in neurological disturbances underlain by the dysregulation of excitatory neurotransmission. Given their therapeutic effectiveness and safety profiles, these in vivo studies need to be further validated, although computational modeling can be further developed for drug design and selectivity. This will open possibilities for new drug-like AMPAR negative allosteric modulators with applications at the clinical level toward neurology.

Machine-Learning-Guided Peptide Drug Discovery: Development of GLP-1 Receptor Agonists with Improved Drug Properties.

Peptide-based drug discovery has surged with the development of peptide hormone-derived analogs for the treatment of diabetes and obesity. Machine learning (ML)-enabled quantitative structure-activity relationship (QSAR) approaches have shown great promise in small molecule drug discovery but have been less successful in peptide drug discovery due to limited data availability. We have developed a peptide drug discovery platform called streaMLine, enabling rigorous design, synthesis, screening, and ML-driven analysis of large peptide libraries. Using streaMLine, this study systematically explored secretin as a peptide backbone to generate potent, selective, and long-acting GLP-1R agonists with improved physicochemical properties. We synthesized and screened a total of 2688 peptides and applied ML-guided QSAR to identify multiple options for designing stable and potent GLP-1R agonists. One candidate, GUB021794, was profiled in vivo (S.C., 10 nmol/kg QD) and showed potent body weight loss in diet-induced obese mice and a half-life compatible with once-weekly dosing.

Developments in the study of Chinese herbal medicine's assessment index and action mechanism for diabetes mellitus.

In traditional Chinese medicine (TCM), based on various pathogenic symptoms and the 'golden chamber' medical text, Huangdi Neijing, diabetes mellitus falls under the category 'collateral disease'. TCM, with its wealth of experience, has been treating diabetes for over two millennia. Different antidiabetic Chinese herbal medicines reduce blood sugar, with their effective ingredients exerting unique advantages. As well as a glucose lowering effect, TCM also regulates bodily functions to prevent diabetes associated complications, with reduced side effects compared to western synthetic drugs. Chinese herbal medicine is usually composed of polysaccharides, saponins, alkaloids, flavonoids, and terpenoids. These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion, enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals. These actions regulate glycolipid metabolism in the body, eventually achieving the goal of normalizing blood glucose. Using different animal models, a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer. Nonetheless, there is a dearth of scientific data about the pharmacology, dose-effect relationship, and structure-activity relationship of TCM and its constituents. Further research into the efficacy, toxicity and mode of action of TCM, using different metabolic and molecular markers, is key to developing novel TCM antidiabetic formulations.

Immunomodulatory of sesquiterpenoids and sesquiterpenoid dimers-based toll-like receptor 4 (TLR4) from Dysoxylum parasiticum stem bark

In recent decades, the interest in natural products with immunomodulatory properties has increased due to their therapeutic potential. These products have a wider range of pharmacological activities and demonstrate lower toxicity levels when compared to their synthetic counterparts. Therefore, this study aimed to investigate the immunomodulatory effects of sesquiterpenoids (SQs) and sesquiterpenoid dimers (SQDs) isolated from Dysoxylum parasiticum (Osbeck) Kosterm. stem bark on human and murine cells, particularly focusing on toll-like receptor 4 (TLR4). Utilizing the secreted alkaline phosphatase (SEAP) assay on engineered human and murine TLR4 of HEK-Blue cells, antagonist TLR4 compounds were identified, including SQs 6, 9, and 10, as well as SQDs 17 and 22. The results showed that 10-hydroxyl-15-oxo-α-cadinol (9) had a potent ability to reduce TLR4 activation induced by LPS stimulation, with minimal toxicity observed in both human and murine cells. The SEAP assay also revealed diverse immune regulatory effects for the same ligand. For instance, SQs 12, 14, and 16 transitioned from antagonism on human to murine TLR4. The SQs (4, 7, 11, and 15) and SQDs (18–20) offered partial antagonist effect exclusively on murine TLR4. Furthermore, these selected SQs and SQDs were assessed for their influence on the production of proinflammatory cytokines TNF-α, IL-1α, IL-1β, and IL-6 of the NF-κB signaling pathway in human and murine macrophage cell lines, showing a dose-dependent manner. Additionally, a brief discussion on the structure-activity relationship was presented.

Phenolic Acid–β-Cyclodextrin Complexation Study to Mask Bitterness in Wheat Bran: A Machine Learning-Based QSAR Study

The need to solvate and encapsulate hydro-sensitive molecules drives noticeable trends in the applications of cyclodextrins in the pharmaceutical industry, in foods, polymers, materials, and in agricultural science. Among them, β-cyclodextrin is one of the most used for the entrapment of phenolic acid compounds to mask the bitterness of wheat bran. In this regard, there is still a need for good data and especially for a robust predictive model that assesses the bitterness masking capabilities of β-cyclodextrin for various phenolic compounds. This study uses a dataset of 20 phenolic acids docked into the β-cyclodextrin cavity to generate three different binding constants. The data from the docking study were combined with topological, topographical, and quantum-chemical features from the ligands in a machine learning-based structure–activity relationship study. Three different models for each binding constant were computed using a combination of the genetic algorithm (GA) and multiple linear regression (MLR) approaches. The developed ML/QSAR models showed a very good performance, with high predictive ability and correlation coefficients of 0.969 and 0.984 for the training and test sets, respectively. The models revealed several factors responsible for binding with cyclodextrin, showing positive contributions toward the binding affinity values, including such features as the presence of six-membered rings in the molecule, branching, electronegativity values, and polar surface area.

3D-QSAR, Scaffold Hopping, Virtual Screening, and Molecular Dynamics Simulations of Pyridin-2-one as mIDH1 Inhibitors

Isocitrate dehydrogenase 1 (IDH1) is a necessary enzyme for cellular respiration in the tricarboxylic acid cycle. Mutant isocitrate dehydrogenase 1 (mIDH1) has been detected overexpressed in a variety of cancers. mIDH1 inhibitor ivosidenib (AG-120) was only approved by the Food and Drug Administration (FDA) for marketing, nevertheless, a range of resistance has been frequently reported. In this study, several mIDH1 inhibitors with the common backbone pyridin-2-one were explored using the three-dimensional structure–activity relationship (3D-QSAR), scaffold hopping, absorption, distribution, metabolism, excretion (ADME) prediction, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, R2 = 0.980, Q2 = 0.765) and comparative molecular similarity index analysis (CoMSIA, R2 = 0.997, Q2 = 0.770) were used to build 3D-QSAR models, which yielded notably decent predictive ability. A series of novel structures was designed through scaffold hopping. The predicted pIC50 values of C3, C6, and C9 were higher in the model of 3D-QSAR. Additionally, MD simulations culminated in the identification of potent mIDH1 inhibitors, exhibiting strong binding interactions, while the analyzed parameters were free energy landscape (FEL), radius of gyration (Rg), solvent accessible surface area (SASA), and polar surface area (PSA). Binding free energy demonstrated that C2 exhibited the highest binding free energy with IDH1, which was −93.25 ± 5.20 kcal/mol. This research offers theoretical guidance for the rational design of novel mIDH1 inhibitors.

Environmental responsive peroxidase-like activity of MoS2@halloysite nanotubes mediated by piezoelectric effect

Nanozymes, as a class of synthetic enzymes, have the characteristics of abundant raw materials and powerful environmental adaptability, potentially serving as substitutes for natural enzymes. Herein, the MoS2 nanosheets were anchored on the surface of alkali activated halloysite nanotubes by utilizing a facile hydrothermal process, resulting in the formation of MoS2@halloysite (MoS2@HNTs) core-shell nanocomposites. The catalytic effect of material on peroxidase under the mechanical stress of applied ultrasonic vibration was systematically investigated with 3,3′,5,5′-tetramethylbenzidine (TMB) as the substrate for chromogenic reaction. The results demonstrated that the established piezoelectric polarization effect generated by MoS2 with asymmetric crystal structure under mechanical force can promote the in-situ coloration of TMB. Concretely, MoS2@HNTs possessing higher Michaels constant (3.42 mmol L-1) and reaction velocity (3.16 × 10–6 mol L-1 min-1) exhibited enhanced peroxidase-like activity compared to pristine MoS2 microspheres. This may be attributed to the fact that halloysite dispersed the MoS2 nanosheets, exposing more reactive sites, and the nanocomposites produced more pronounced structural deformation under mechanical stress. The detailed experiments and theoretical calculation have elucidated the structure-activity relationship and microscopic mechanism among the microstructures, piezoelectric polarization effects and peroxidase catalytic effects of materials. This work provides an advanced prototype for the research of environmental responsive enzyme-like catalytic effects of mineral-based nanozymes with the regulation of external environmental factors.

Catalytic cycle network: Boosting CO2 hydrogenation to propane

The utilization of CO2 hydrogenation to manufacture high-value chemicals is a viable strategy for achieving carbon neutrality. However, the reaction mechanisms still need to be further developed to improve catalytic efficiency. In this context, we report a bifunctional ZnZrOx/SSZ-13 catalyst, the conversion of CO2 reached 44.7 %, while the selectivity for CO was maintained at 16.7 %, and remarkably, the selectivity and yield for propane increased to 70.3 % and 26.1 %, respectively. A “catalytic cycle network” that involve H2O generated in situ by tandem reaction is suggested, and its mechanism confirmed through in situ DRIFTS spectroscopy, density functional theory (DFT) calculations, studies on water diffusion, and empirical evidence. This innovative mechanism, which departs from traditional tandem catalysis, signals a paradigm shift in the field of catalytic chemistry. At low space velocities, water generated during the reaction contributes by mass transfer diffusion to promote the tandem reactions. This phenomenon establishes a positive feedback loop in which “reaction-produced H2O promotes the reaction” and integrates with tandem reactions to form a “catalytic cycle network”. Such complex, multi-level interactions significantly improve the hydrogenation of CO2. Subsequent studies of the structure-activity relationship between zeolite properties and bifunctional catalyst performance reveal a synergistic effect of zeolite acidity and hydrophobicity on reaction performance, which together determine the efficiency of the reaction. These findings provide a solid foundation for the design of effective catalysts for CO2 hydrogenation and have the potential to transform the field, thereby making a significant contribution to sustainable chemical synthesis.

New Strategies for Responding to SARS-CoV-2: The Present and Future of Dual-Target Drugs.

The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths, posing a serious threat to public health and safety. Rapid mutations of SARS-CoV-2 and complex interactions among multiple targets during infection pose a risk of expiry for small molecule inhibitors. This suggests that the traditional concept of "one bug, one drug" could be ineffective in dealing with the coronavirus. The dual-target drug strategy is expected to be the key to ending coronavirus infections. However, the lack of design method and improper combination of dual-targets poses obstacle to the discovery of new dual-target drugs. In this Perspective, we summarized the profiles concerning drug design methods, structure-activity relationships, and pharmacological parameters of dual-target drugs for the treatment of COVID-19. Importantly, we underscored how target combination and rational drug design illuminate the development of dual-target drugs for SARS-CoV-2.

Disposal of spent V2O5-WO3/TiO2 catalysts: A regeneration principle based on structure-activity relationships from carrier transformations

Characterization and evaluation of hazardous spent V2O5-WO3/TiO2 catalysts are critical to determining their treatment or final disposal. This study employs a thermal approach to simulate the preparation of spent catalysts derived from commercial V2O5-WO3/TiO2 catalysts and investigate the structure-activity relationship of the carrier changes during the deactivation process. The results indicate that the catalyst carrier undergoes two processes: an increase in grain size and a transformation in crystal structure. Both structural and catalytic investigations demonstrate that the grain size for catalyst deactivation is 24.62 nm, and the formation of CaWO4 occurs before the crystalline transformation. The specific surface area is susceptible to an increase in grain size. The reactions of selective catalytic reduction involve the participation of both Brønsted acid and Lewis acid sites. The deactivation process of the carrier initially affects Brønsted acid sites, followed by a reduction in Lewis acid sites, resulting in a decline in NH3 adsorption capacity and oxidation. Correlation analysis reveals that changes in the physicochemical properties of the catalyst reduce the NO conversion, with the order being The grain size > Total acid amount > The surface area. It is recommended to recycle the spent catalyst if the carrier grain size is less than 25 nm. The findings of this investigation contribute to expanding the database for evaluating and understanding the physicochemical properties of spent catalysts for disposal.