Current drug discovery technologies最新文献

Introduction: African swine fever virus (ASFV) is the causative agent of African swine fever, a highly lethal disease affecting domestic pigs and wild boars. Despite its first identification in East Africa in the early 1900s, no effective therapeutic drugs or vaccines are currently available. This study investigates the inhibitory potential of red algae-derived compounds against ASFV dUTPase, a key enzyme that prevents uracil misincorporation during viral DNA synthesis and maintains ge-nome fidelity.

Methods: Red algal compounds were curated from an extensive database and subjected to ADMET analysis to evaluate their pharmacokinetic properties. Binding interactions with ASFV dUTPase were analyzed using a consensus docking approach. Molecular dynamics simulations and binding free en-ergy calculations were then conducted to assess the stability and energetic favorability under swine physiological conditions. Off-target docking was performed to identify potential interactions with swine dUTPase and evaluate safety.

Results: Among the compounds tested, thyrsenol A and 14-keto-dehydro-thyrsiferol, isolated from two Laurencia species, were identified as promising inhibitors of ASFV dUTPase. Both compounds demonstrated stable binding interactions with the target protein and strong binding affinities. Analy-sis of RMSD, RMSF, and hydrogen bond profiles further supported their stability. Off-target analysis indicated a low likelihood of interfering with swine dUTPase function.

Conclusion: These findings highlight red algae as a potential source for developing anti-ASFV ther-apeutics and pig feed supplements. Further in vitro and in vivo studies are warranted to validate these results and explore their practical applications in disease control.

Introduction: Chronic wounds, including diabetic foot ulcers and pressure ulcers, are significant clinical challenges due to impaired healing caused by chronic inflammation, poor angiogenesis, and Extracellular Matrix (ECM) abnormalities. These wounds impose a substantial socio-economic burden worldwide, necessitating innovative therapeutic strategies. This review explores the integration of cyclic peptides into hydrogel dressings as an advanced approach to improve wound healing outcomes, particularly in chronic wounds unresponsive to traditional treatments.

Methods: The study looks at several strategies for integrating cyclic peptides into hydrogel matrices, including physical entrapment, covalent conjugation, self-assembly, layer-by-layer assembly, and microencapsulation. It also examines preclinical and clinical evidence supporting the effectiveness of cyclic peptide-loaded hydrogels in wound healing.

Results: Cyclic peptide-loaded hydrogels demonstrate enhanced biological activity compared to linear peptides, exhibiting superior stability, membrane permeability, receptor binding affinity, and reduced immunogenicity. These hydrogels provide multifaceted therapeutic effects, including antimicrobial activity, modulation of inflammation, promotion of angiogenesis, ECM remodeling, and enhanced re-epithelialization. Preclinical models, including diabetic, septic, burn, and ischemic wounds, show accelerated healing, reduced bacterial load, and improved tissue regeneration.

Discussion: Early clinical studies report significant reductions in healing times and increased wound closure percentages. Controlled release systems enable fine-tuning of peptide delivery to match the needs of the wound microenvironment. Despite promising results, issues such as peptide stability, scalable manufacturing, regulatory complexity, and production costs must be addressed before wider clinical adoption. The paper highlights emerging technologies like stimuli-responsive hydrogels, designer cyclic peptides, integration with cell therapies, wearable sensor platforms for real-time monitoring, and 3D bioprinting for personalized wound dressings. Mechanistic studies and precision medicine approaches are encouraged to optimize therapeutic efficacy.

Conclusion: The combination of cyclic peptides and hydrogel technology is a potential strategy for increasing wound healing, especially for chronic wounds that do not heal with standard methods. However, stability, manufacturing, and regulatory issues must be overcome before widespread clinical use can occur. Future research directions include personalized approaches, integration with cell therapies, and mechanistic studies to improve the efficacy of these wound-healing systems.

Introduction: The blood-brain barrier (BBB) severely restricts drug delivery to the central nervous system (CNS). Early, accurate in silico prediction of BBB permeability is a critical challenge in drug discovery. This study aimed to develop, validate, and optimize a robust machine learning framework for this task, with a specific focus on enhancing a Deep Neural Network (DNN) model using a bio-inspired Ant Colony Optimization (ACO) algorithm.

Methods: A dataset of 1957 compounds was curated and characterized by 212 molecular descriptors. The dataset was partitioned using a scaffold-based split. A suite of baseline models (Naive Bayes, k-NN, SVM, Random Forest, XGBoost, and a baseline DNN) was benchmarked. An ACO algorithm was then implemented to perform a systematic hyperparameter search for the DNN. The performance of all models was evaluated on an independent test set.

Results: The Random Forest model provided a strong baseline performance (AUC = 0.913). The ACO algorithm identified a superior DNN architecture. The final ACO-Optimized DNN achieved a state-of-the-art performance on the independent test set, with an AUC-ROC of 0.921, outperforming all baseline classifiers. An error analysis of misclassified compounds provided insights into the model's limitations.

Discussion: The successful performance gain highlights the advantage of metaheuristic optimization over traditional hyperparameter search approaches. The model demonstrated stability and strong generalization.

Conclusion: The ACO-Optimized DNN provides a highly accurate tool for virtual screening in CNS drug discovery, and the methodology serves as a generalizable template for complex model optimization.

Introduction: GPER1 belongs to the large GPCR family, known for its diverse biological functions and therapeutic value in multiple diseases. It has gained attention for its role in mediating estrogenic signaling pathways, which exert protective and beneficial effects in disease. The current study aims to identify potential compounds for effective therapies targeting GPER1 employing in silico approaches.

Methods: This study integrates a suite of computational techniques, including molecular modeling, pharmacophore-based virtual screening, docking studies, and molecular dynamics simulations, to analyze structural dynamics, functional relevance, and potential therapeutic applications. Ligand Scout was used to construct the pharmacophore models of reported inhibitors and drugs retrieved before the virtual screening. RMSD, RMSF, and B-factor graphs are generated through simulations for 50 nanoseconds to reveal the structural features of the GPER1 model.

Results: The comparative modeling approach was applied to build the GPER1 3D model, yielding an overall quality factor of 89%. Energy minimization and simulations for structure optimization were followed until a 92% quality factor was attained. Two novel leads, ZINC39470612 and ZINC72326045, appeared to have maximum binding affinities, i.e., 63.4983 and 58.87, respectively, with the GPER1 receptor. Post-docking analyses identified Phe-98, Met-260, Tyr-324, and Leu-327 as crucial residues for the effective drug therapies targeting GPER1.

Conclusion: Extensive analyses have demonstrated that ZINC39470612 and ZINC72326045 are identified as potential compounds for targeting GPER1. These compounds also exhibited better binding affinities and ADME features than reported drugs and inhibitors. These in silico findings provide critical structural and functional insights with promising therapeutic relevance.

Background: The N-methyl-D-aspartate receptor (NMDAR) plays a critical role in regulating excitatory glutamatergic neurotransmission and synaptic plasticity. However, ex-cessive NMDAR activation can lead to increased calcium ion influx, resulting in excitotoxi-city-a key contributor to neurodegenerative diseases. Although current NMDAR inhibitors exist, their clinical use is limited due to adverse effects.

Methods: This study employed computational screening of Bacillus-derived macrolactins to identify potential NMDAR antagonists. Molecular docking simulations were performed using AMDock v1.5.2 with the AutoDock Vina engine to assess binding affinities to NMDAR (PDB:7SAD). Docked complexes were analyzed for chemical interactions, including polar contacts, using PyMol v2 and Discovery Studio Visualizer v4.5. Pharmacokinetic properties of macrolactins were predicted using Deep-PK. Molecular dynamics simulations via GROMACS assessed complex stability through RMSD, RMSF, radius of gyration (Rg), hy-drogen bond count, and solvent-accessible surface area (SASA). Network pharmacology anal-ysis of macrolactins in Alzheimer's disease (AD) involved mapping target interactions in STRING, importing into Cytoscape, and identifying hub genes using CytoHubba for KEGG pathway enrichment.

Results: Macrolactin F emerged as a promising candidate, exhibiting strong binding affinity (-6.8 kcal/mol) and an estimated Ki of 10.37 μM, outperforming commercial memantine and other macrolactins. Molecular dynamics simulations confirmed the stability and conforma-tional integrity of the Macrolactin F-NMDAR complex. KEGG pathway enrichment analysis highlighted key hub pathways associated with AD, including hsa05010, hsa04725, hsa04722, hsa04071, hsa04068, hsa04150, and hsa04910.

Discussion: The findings suggest that Macrolactin F possesses superior antagonistic activity against NMDAR compared to memantine, supported by molecular docking and dynamic sim-ulations. Network pharmacology analyses indicate that Macrolactin F can modulate critical signaling pathways implicated in AD, including PI3K/Akt/mTOR and MAPK cascades.

Conclusion: Computational analyses identify Macrolactin F as a promising preclinical candi-date for developing allosteric NMDAR inhibitors. This aligns with SDG 3 by contributing to potential therapeutics for neurodegenerative diseases such as Alzheimer's disease and supports SDG 10 by promoting accessible interventions to reduce global health disparities.

Introduction: A frequent superficial fungal infection that affects keratinized tissues such as the skin, hair, and nails is dermatophytosis, sometimes referred to as ringworm. Microsporum, Epidermophyton, and Trichophyton species are the main causes of disease. Effective disease man-agement still requires an understanding of the epidemiology and modes of transmission of these illnesses. This study aims to present an in-depth analysis of dermatophytosis with an emphasis on the organisms that cause it, diagnostic techniques, treatment plans (both traditional and innovative), preventative techniques, and the most recent medicinal developments.

Methodology: Elsevier, Google Scholar, ScienceDirect, PubMed, and other scientific literature databases were thoroughly searched to obtain current and pertinent information. Analysis and discussion were conducted on studies that addressed the causes, transmission, diagnostic processes, treatment options (both traditional and innovative), and preventive measures for ringworm infection.

Result: Management of dermatophytosis includes both conventional and advanced therapeutic approaches. Conventional treatment usually involves the application of topical antifungal agents (such as clotrimazole, terbinafine, or miconazole, etc.) and, in more severe or widespread infections, systemic antifungal therapy (such as oral Itraconazole or Griseofulvin). In recent years, significant progress has been made in the development of advanced drug delivery systems aimed at enhancing drug retention, efficacy, and patient compliance.

Discussion: The present review discussed the management of ringworm infection, such as topical or oral conventional treatment, advanced drug delivery techniques (solid lipid nano-particals and liposomes, etc), and some of them are herbal remedies.

Conclusion: A multidisciplinary and integrative approach that combines conventional antifungal therapy with advanced delivery systems and natural remedies yields improved outcomes in the management of dermatophytosis. Understanding the disease's transmission dynamics and epidemiological trends is essential for timely diagnosis, effective treatment, and prevention of recurrence. Preventive strategies, including hygiene education, proper skin care, and early treatment of infections, are critical components in controlling the spread of dermatophyte infections within communities.

Introduction: Syzygium jambolanum has long been used to treat diabetes mellitus in herbal therapy. Scientists are interested in confirming its effectiveness in reducing blood glucose and enhancing metabolic parameters through clinical and biochemical evaluations.

Methods: Groups of people with diabetes who were receiving treatment and those who were not were separated. Supplementation with Syzygium jambolanum was given to the treatment group. Fasting Blood Glucose (FBG), HbA1c, SGPT, SGOT, serum urea, Blood Urea Nitrogen (BUN), uric acid, alkaline phosphatase, total cholesterol, HDL cholesterol, and creatinine were among the biochemical markers that were evaluated.

Results: When compared to the untreated group, the treated group's fasting blood glucose levels were significantly lower. Indicating improved glycaemic control and organ function, the treated group also showed notable improvements in other indicators, including HbA1c, SGPT, SGOT, serum urea, BUN, uric acid, alkaline phosphatase, total cholesterol, HDL cholesterol, and creatinine.

Discussion: Syzygium jambolanum extracts show strong antidiabetic effects by lowering blood glu-cose and enhancing insulin activity. Their rich antioxidant content protects pancreatic β-cells from oxidative stress. Overall, the extracts help improve glycemic control and metabolic health in diabetic conditions.

Conclusion: Syzygium jambolanum exhibits a potent antidiabetic action, markedly lowering blood sugar levels and biochemical indicators linked to problems from diabetes. It might work well as a natural supplement to help control diabetes.

The main objective of this review is to evaluate the biomedical potential of silver nano-particles (NPs) synthesized using the medicinal plant Scrophularia striata Boiss. (S. striata), known for its traditional use in Asian folk medicine and for its promising pharmaceutical potential, achieved through an eco-friendly, sustainable green synthesis approach. S. striata serves as a potent natural reducing and stabilizing agent for silver NP formation under controlled conditions. The resulting NPs are characterized using a range of spectroscopic and microscopic techniques. Studies have reported average particle sizes ranging from 10 to 40 nm, exhibiting consistent morphology, notable stability, and excellent biocompatibility. These green-synthesized NPs have demonstrated significant antioxi-dant activity, broad-spectrum antimicrobial effects, as well as anti-inflammatory and anticancer prop-erties. This review highlights the promising biomedical applications of S. striata-derived silver NPs and underscores their potential role in advancing future therapeutic research and clinical translation. Their potential role in advancing future therapeutic research and clinical translation.

Introduction: Vitamins are essential for maintaining wellness since they are involved in several distinct physiological functions. In addition to being necessary for the methylation cycle and the creation of monoamine oxidase, vitamin B complex is also required for deoxyribonucleic acid synthesis, phospholipid preservation, and repair. Vitamin B deficiency or excess may affect dementia, cognitive decline, and memory. Deficits in these vitamins, particularly B12 (cobalamin, or vitamin B12), are therefore strongly linked to depression. Cyanocobalamin is used to assist in managing deficiencies, available as nasal spray, injection, and oral supplements. Chemically, cyanocobalamin is classified as a "corrinoid," which refers to a cobalt complex that may crystallize. The FDA of the United States has licensed cyanocobalamin for the treatment of Helicobacter pylori infection, atrophic gastritis, malabsorption, depression, autoimmune anemia, and other disorders.

Method: Information from in vivo, in silico, and clinical trials was gathered for this review from sources such as Google Scholar, ScienceDirect, and PubMed. The antidepressant properties of vitamin B12 derived from Hippophae rhamnoides were the primary focus.

Results: Research indicates that cyanocobalamin modulates inflammation, oxidative stress, and serotonin and dopamine pathways. It enhances treatment responsiveness and reduces depression symptoms when used alongside conventional antidepressants.

Discussion: Vitamin B12's significance in energy metabolism and antioxidant defense complements its neurochemical benefits. The natural cyanocobalamin source, Hippophae rhamnoides, offers a unique treatment approach that may improve mood and protect neurons.

Conclusion: Based on these studies, it was concluded that vitamin B12 may delay depression onset and enhance the effectiveness of antidepressants. Other vitamins, such as vitamin B6 (pyridoxine) and B9 (folate), also influence depression. However, in this study, we first focused on the effect of vitamin B12 from Hippophae rhamnoides on depression and neurochemical pathways. The review article was generated by analyzing data and studies to establish the correlation between vitamin B12 and depression.

Introduction: The inflamed, symmetrical, persistent autoimmune condition, rheu-matoid arthritis, starts small and gradually spreads to bigger joints. It may damage joints and internal organs resulting in permanent impairment. The treatment of rheumatoid arthritis by natural products focusing on inflammatory cytokines is mentioned.

Methods: The data for this study were found on PubMed, Google Scholar, ACS Publishing Centre, Springer Nature, Bentham Science, PLOS One, MDPI, Cochrane Library, Web of Sci-ence, Scopus, and MEDLINE. The electronic databases were used to search literature pub-lished after 2021.

Results: The progressive development of joint deterioration is prevented by early therapy. Pathophysiology of RA in patients has been largely emulated in the experimental model of arthritis induced with CFA, and this has allowed the evaluation of the efficiency of natural products, such as extracts of medicinal plants, metabolites isolated from them, and even bio-active nanoparticles. The effect of arthritic illness has been effectively slowed down by natural extract, dietary phenolic substances metabolite, whereas the nanoparticles overcome the bioa-vailability.

Discussion: The management of illness is the main focus of the majority. Cost, mode of ad-ministration, safety, and efficacy have a significant role in influencing patient choice. Natural products and nanoparticles possess efficient interaction with the body microbiota to maintain health and prevent disease.

Conclusion: Nanotechnology possesses inflammatory action via various mechanisms, i.e. VEGF, MMP2, MMP3, TNFα, NF-κB, IL1β, IL6, to provide fascinating new understandings of its anti-inflammatory, antioxidant, and immunomodulatory characteristics. Numerous ex-tracts and phytochemicals are reported in CFA-induced arthritis. This article discusses the pathophysiology, risk factors and treatment, focusing on natural products and nanotechnology.