Current pharmaceutical design最新文献

{"title":"Therapeutic Potential of Menstrual Blood-Derived Stem Cells in Attenuating Uterine Adhesion: Novel Strategies and Future Prospect.","authors":"Yasamin Rajabloo, Abdulridha Mohammed Al-Asady, Amir Avan, Majid Khazaei, Mikhail Ryzhikov, Seyed Mahdi Hassanian","doi":"10.2174/0113816128348717250108184050","DOIUrl":"https://doi.org/10.2174/0113816128348717250108184050","url":null,"abstract":"<p><p>Intrauterine Adhesions (IUAs) are characterized by endometrial damage due to endometritis or curettage. Currently, the gold standard for IUA treatment is hysteroscopy, which enables the dissolution of IUA through mechanical or electrosurgical energy. Common strategies to prevent recurrence include the insertion of a balloon catheter or IUD in the uterus. Although hysteroscopy and postoperative strategies improve the uterine cavity's morphology and menstrual flow in some patients, infertility and adhesion recurrence rates are among the problems that persist. Mesenchymal Stem Cells (MSCs) are ideal for tissue regeneration due to their self-renewal and immunomodulatory characteristics. MSCs also exert anti-fibrotic properties in IUA treatment. However, the clinical application of stem cells is limited due to safety concerns and cost. In this review, we have summarized the recent advances in the application of MSCs in IUA treatment.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Tagging Technology of Exosomes- An Updated Review.","authors":"Aniruddha Sen, Palani Selvam Mohanraj, Srinivas Nagaram, Anita Samanta, Sumel Ashique, Anas Islam, Shriyansh Srivastava, Harpreet Singh, Arun Kumar Mishra, Shivani Chopra, Hitesh Chopra","doi":"10.2174/0113816128338023241210140702","DOIUrl":"https://doi.org/10.2174/0113816128338023241210140702","url":null,"abstract":"<p><p>Exosomes are small extracellular vesicles secreted by various cell types, playing a crucial role in intercellular communication by carrying proteins, lipids, and nucleic acids, thus holding significant potential in diagnostics and therapeutics. Accurate labeling of exosomes is vital for studying their biogenesis, trafficking, and functional properties, enabling precise tracking and manipulation. This review examines current labeling techniques, including metabolic glycan labeling, chemical tagging, membrane fluorescent dyes, bio-conjugation, non-covalent labeling, and cell-engineering approaches. Each method is analyzed for its efficiency, specificity, and practicality, with attention to potential artifacts and challenges. Advancements in these techniques are essential for improving our understanding of exosome biology and developing exosome-based diagnostic and therapeutic strategies, providing researchers with valuable insights into state-of-the-art techniques and their applications in exosome research.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology, Molecular Docking, Molecular Dynamics to Explore the Mechanism of Danggui Shaoyao Powder for Hepatic Encephalopathy.","authors":"Miao Zhang, Rongxin Liu, Yusen Zhao, Zixin Chen, Honglin Zhai, Hongzong Si","doi":"10.2174/0113816128363445241218062155","DOIUrl":"https://doi.org/10.2174/0113816128363445241218062155","url":null,"abstract":"<p><strong>Background: </strong>Patients with hepatic encephalopathy (HE) have many triggers and a high mortality rate. The protective effect of existing therapeutic drugs on the liver is weak. We found that Danggui Shaoyao Powder can improve the symptoms of HE and may have a better liver protection effect. And the mechanism of it is unclear.</p><p><strong>Objective: </strong>The research explores the mechanism of Danggui Shaoyao Powder for the treatment of HE through network pharmacology, molecular docking and molecular dynamics.</p><p><strong>Methods: </strong>Targets of Danggui Shaoyao Powder were screened from Traditional Chinese Medicine System Pharmacology Platform (TCMSP), SwissTargetPrediction, and Uniport. GeneCards was used to gain targets of HE. Further, core targets and ingredients were screened by protein-protein interaction network (PPI) and herbs-compounds-targets network. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were completed to screen relative sites and signaling pathways. Molecular docking and dynamics were used to show the stability of ligand-receptor complexes.</p><p><strong>Results: </strong>IL6, SRC and kaempferol, beta-sitosterol were screened as the top two core targets and ingredients. Dendrites, dendritic trees, and membrane sides were defined as the main sites of action. Core signaling pathways were screened such as: PI3K-Akt and MAPK. Molecular docking shows well-defined binding sites and the stability of the binding is demonstrated by molecular dynamics.</p><p><strong>Conclusion: </strong>Through this study, Danggui Shaoyao Powder may act on IL6, SRC, and other targets through ingredients such as kaempferol and beat-sitosterol and regulate signaling pathways such as PI3K-Akt, MAPK and NF-κB to the treatment of HE.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Therapeutic Potential of the Methanolic Extract and Fractions of Datura stramonium in Paracetamol-intoxicated Rabbits.","authors":"Mohammad Attaullah, Hussain Ul Haq, Abdullah Khan, Bashir Ahmad, Alaa Alhegaili, Muhammad Hamayun, Sajid Ali","doi":"10.2174/0113816128365599241226113546","DOIUrl":"https://doi.org/10.2174/0113816128365599241226113546","url":null,"abstract":"<p><strong>Introduction: </strong>Datura stramonium (DS) possesses strong medicinal and therapeutic potential but has been rarely evaluated in this context.</p><p><strong>Methods: </strong>The present study was intended to evaluate the antioxidant, hepatoprotective, and nephroprotective potential of the crude methanolic leaf extract and ethyl acetate, chloroform, n-hexane, and aqueous fractions of DS in paracetamol-intoxicated rabbits. Paracetamol (2 g/Kg BW) was applied to induce liver and kidney injury in rabbits while the methanolic extract and fractions of DS were applied in the dose range of 150 mg/Kg to 300 mg/Kg body weight for 21 days. Histopathology of the liver, and kidney and analysis of ALT (Alanine Transaminase), ALP (Alkaline Phosphatase), total bilirubin, serum urea, serum creatinine, and serum uric acid were carried out. In-vitro antioxidant potential of the extract and fractions of DS was carried out through DPPH (1,1-diphenyl 2-picrylhydrazyl) free radical scavenging assays.</p><p><strong>Results: </strong>The hepatoprotective and nephroprotective potential of the extract and fractions of DS at the dose level of 300 mg/Kg BW was highly significant (P ˂ 0.01). ALT was found elevated in the paracetamol-treated group (117.3 ± 1.61 U/L) compared to the group treated with methanolic extract of DS, (57.3 ± 0.87 U/L) and normal control group (60.6 ± 1.58 U/L) at 300 mg/kg BW. Elevated levels of ALP (120 ± 1.58 U/L) and Bilirubin (1.6 ± 0.32 mg/dl) were found in the paracetamol-treated group compared with the group treated with methanolic extract of DS (67.5 ± 1.35 U/L; 0.2 ± 1.0 mg/dl) and normal control group (70.1 ± 1.53 U/L; 0.4 ± 0.16 mg/dl) respectively at 300 mg/kg BW. The methanolic extract of DS produced a marked scavenging activity of the DPPH free radicals (88.2 ± 0.006 %) followed by the fractions of DS compared to ascorbic acid (95.5 + 0.003 %) at a concentration of 1000 μg/ml. The effects were comparable to those produced by ascorbic acid. Liver and kidney histology of the rabbits treated with extract, fractions, and ascorbic acid of DS caused reductions in the pathological features compared to the paracetamol-treated animals. The histological observations and chemical pathological alterations demonstrated the significant hepatoprotective and nephroprotective benefits of the DS extract and its fractions.</p><p><strong>Conclusion: </strong>It has been concluded that the methanolic extract and fractions of DS possess antioxidant, hepatoprotective, and nephroprotective properties in paracetamol-intoxicated rabbits.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALS: A Silent Slayer of Motor Neurons. Traditional Chinese Herbal Medicine as an Effective Therapy.","authors":"Anjali Rai, Shivang Shukla, Ramesh Kumar Gupta, Anuradha Mishra","doi":"10.2174/0113816128329141241205063352","DOIUrl":"https://doi.org/10.2174/0113816128329141241205063352","url":null,"abstract":"<p><p>Amyotrophic Lateral Sclerosis (ALS), is a progressive neurodegenerative disease characterized by motor symptoms, and cognitive impairment. The complexity in treating ALS arises from genetic and environmental factors, contributing to the gradual decline of lower and upper motor neurons. The anticipated pharmaceutical market valuation for ALS is projected to reach $1,038.94 million by 2032. This projection underscores the escalating impact of ALS on global healthcare systems. ALS prevalence is expected to surge to 376,674 cases by 2040. In 2022, India ranked among the top 3 Asian-Pacific nations, while North America dominated the global ALS market. Ongoing investigations explore the potential of neuroprotective drugs like riluzole and edaravone in ALS treatment. Recently approved drugs, Relyvrio (sodium phenylbutyrate and taurursodiol) and Tofersen (Qalsody) have completed the trials, and others are currently undergoing extensive clinical trials. Continuous research and exploration of therapeutic avenues, including gene therapy and neuroprotective treatments, are imperative to address the challenges posed by ALS and other neurodegenerative diseases. Traditional Chinese Medicine (TCM) approaches and clinical trials are being explored for treating ALS symptoms, targeting neuroinflammation, oxidative damage, and muscle weakness, showcasing the potential benefits of integrating traditional and modern approaches in ALS management.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auranofin-loaded PLGA Nanoparticles for Neuroprotection against Aluminium-induced Alzheimer's Disease.","authors":"Shiv Kumar Kushwaha, Mahendra Singh Ashawat, Rimpi Arora, Ashish Baldi","doi":"10.2174/0113816128336703241202182209","DOIUrl":"https://doi.org/10.2174/0113816128336703241202182209","url":null,"abstract":"<p><strong>Aim: </strong>The aim of the current study was to explore nano-formulation for effective neuroprotection by auranofin.</p><p><strong>Background: </strong>Currently, the treatment options for various CNS disorders, particularly neurodegenerative disorders, are greatly constrained. A significant obstacle in this pursuit is the blood-brain barrier, a shielding covering that hinders the route of numerous biochemical treatments into the brain. To overcome this problem, nanoformulation- based approaches are gaining interest, increasing the compound's BBB penetrability.</p><p><strong>Objective: </strong>The objective of this study was to evaluate whether nanoparticles fabricated from poly(lactic-co-glycolic acid) encapsulated with auranofin could oppose aluminium chloride-induced Alzheimer's disease.</p><p><strong>Method: </strong>Auranofin-encapsulated PLGA nanoparticles were prepared, and their particle size, Entrapment Efficiency (EE), distribution of particles, morphological surface charge, and structural characteristics were characterized. During the in vivo study, rats were orally administered AlCl3 at 100 mg/kg for 21 days. Meanwhile, auranofin and auranofin nanoparticles were orally administered at doses of 5 and 10 mg/kg and 2.5 and 5 mg/kg, respectively, within 2 weeks. After the course therapy, the rats were decapitated, and the hippocampus was collected for the estimated biochemical and neuroinflammatory markers.</p><p><strong>Results: </strong>The auranofin nanoparticles were characterized, revealing % entrapment efficiency (98%) and % loading dose (76%). The nanoparticles exhibited a morphological surface charge of 27.5 ± 5.10 mV, a polydispersity index of 0.438 ± 0.12, and a mean particle size of 101.5 ± 10.3 nm. In the in vivo study, administering a gold compound (auranofin) and formulation (auranofin nanoparticles) resulted in a significant improvement in cognitive deficits, changes in biochemical parameters, and markers of neuroinflammation triggered with aluminium chloride.</p><p><strong>Conclusion: </strong>The results have suggested that auranofin nanoparticles demonstrate abilities to protect neurons compared to auranofin alone. The noticed therapeutic benefits of the auranofin-encapsulated PLGA nanoparticles can be attributed to modulation in particle size with antioxidative and anti-inflammatory impacts of auranofin. Consequently, the outcome of the research has revealed that gold compound nanoparticles hold the potential to be a promising option for altering the therapeutic course of Alzheimer's disease.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic Cannabinoids are Genotoxic in Cultured Human Lymphocytes.","authors":"Alla Abdulwahab Almestafa, Omar Falah Khabour, Laith Naser Al-Eitan, Karem Hasan Alzoubi","doi":"10.2174/0113816128340465241227095853","DOIUrl":"https://doi.org/10.2174/0113816128340465241227095853","url":null,"abstract":"<p><strong>Background: </strong>Synthetic cannabinoids are one of the most identified abused drugs nowadays. Their popularity is due to their psychoactive effects, which resemble delta 9 tetrahydrocannabinol. This study investigates the genotoxic potential of three synthetic cannabinoids of indazole-passed drugs, AB-Fubinaca, AMBFubinaca, and EMB-Fubinaca (at a final concentration of 200 nM).</p><p><strong>Methods: </strong>Genotoxicity was examined using Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays in cultured human lymphocytes. Blood for lymphocyte cultures was obtained from healthy adult young males.</p><p><strong>Results: </strong>A significant increase in the frequency of SCEs was detected for all examined drugs (range: 5.4-6.1, p < 0.05) compared to the control group (4.70 ± 0.31). The order of synthetic cannabinoids in terms of their ability to induce SCEs was EMB-Fubinaca (6.04 ± 0.63) > AMB-Fubinaca (5.65 ± 0.6) > AB-Fubinaca (5.33 ± 0.58). None of the examined drugs induced significant changes to the frequency of CAs (p > 0.05). Additionally, there were no effects of the synthetic cannabinoids at the studied concentration on proliferation and mitotic indices.</p><p><strong>Conclusion: </strong>Synthetic cannabinoids have been found to increase the frequency of SCEs in cultured human lymphocytes. The results should be confirmed in in vivo studies using lymphocytes derived from synthetic cannabinoid users.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the cGAS-sting Pathway Mediated by Nanocomplexes for Tumor Therapy.","authors":"Yuxuan Qian, Shujuan Cao, Li He, Yanfei Cai, Zhaoqi Yang","doi":"10.2174/0113816128339788241221160639","DOIUrl":"https://doi.org/10.2174/0113816128339788241221160639","url":null,"abstract":"<p><p>cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway is an natural immune response signaling pathway in the human body that is essential for sensing abnormal DNA aggregation in the cell. When the cGAS protein senses abnormal or damaged DNA, it forms a second messenger called cyclic dinucleotide (cGAMP). The cycled dinucleotide will activate the downstream STING protein, thereby inducing the expression of inflammatory cytokines such as type I interferon, which binds to receptors on its own cell membrane and ultimately initiates multiple immune response pathways. This signaling pathway plays an important immune role in antimicrobial and antitumor functions, etc. so the development of drugs targeting this signaling pathway has important clinical application value. In recent years nanocomplexes based cGAS-STING signaling pathway activation and inhibition treatments have been gradually developed. In this review, on the basis of elaborating the main activation mechanism of the cGAS-STING pathway, we further introduced the nanocomplexes that effectively activate the cGAS-STING pathway, focusing on the composition, types and applications of the nanocomplexes. In addition, we discussed the key challenges and future research directions of the way that stimulating the cGAS-STING signaling pathway in the form of nanocomplexes to activate immuno-tumor therapy. Our work aims to provide a better understanding of the progress of nanotherapeutics in the cGAS-STING pathway, providing a promising anti-tumor therapeutic strategy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Therapeutic Potential of Sophora flavescens Aiton in Myocardial Infarction: An Integrative Approach Combining Bioinformatics, Network Pharmacology, and Experimental Validation.","authors":"Zhongbai Zhang, Yang Tong, Hongwei Xie, Mengting Jiang, Yanchun Li, Chun Liang","doi":"10.2174/0113816128342405241204055321","DOIUrl":"https://doi.org/10.2174/0113816128342405241204055321","url":null,"abstract":"<p><strong>Aims: </strong>This study aims to elucidate the relationship between potential MI targets and SFA's mechanism of action, providing a theoretical basis for clinical development of new drugs.</p><p><strong>Background: </strong>Myocardial infarction (MI) has been identified as one of the major cardiovascular diseases with adverse consequences. Sophora flavescens Aiton (SFA) is indicated for the therapeutic treatment of MI. However, there is no systematic research on the new therapeutic targets for MI and the exact action mechanism of SFA.</p><p><strong>Objective: </strong>This study explores the potential mechanisms of SFA in treating MI by integrating bioinformatics, network pharmacology analyses and experimental verification.</p><p><strong>Methods: </strong>New MI targets were predicted using bioinformatics techniques. Network pharmacology and molecular docking jointly served for predicting the key targets and underlying mechanisms of SFA. A machine learning model was developed to identify the core MI targets. Subsequently, H9c2 cardiomyocytes hypoxia model was established for experimental verification.</p><p><strong>Results: </strong>140 active components were ascertained in SFA and 59 differentially expressed genes (DEGs) were screened for MI. Eighty-seven shared genes were obtained by WGCAN. Eighty proteins and 413 interactions were identified by PPI network. After building the machine model, three core targets were identified (STAT1, TNFRSF1A and MCL1). According to in vitro experiments, SFA exerts a protective effect relying on three core targets and biological processes, including cell viability, the inflammatory response, and antiapoptotic effects, etc. Conclusion: This study finds new core targets for MI and the therapeutic activity of SFA against MI, of which the experimental verification provides valuable insights into the molecular mechanisms underlying SFA's efficacy in MI treatment and paves the way for targeted drug development strategies.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing COVID-19 Treatment: The Role of Non-covalent Inhibitors Unveiled by Integrated Machine Learning and Network Pharmacology.","authors":"Saba Qadir, Fahad M Alshabrmi, Faris F Aba Alkhayl, Aqsa Muzammil, Snehpreet Kaur, Abdur Rehman","doi":"10.2174/0113816128342951241210175314","DOIUrl":"https://doi.org/10.2174/0113816128342951241210175314","url":null,"abstract":"<p><strong>Introduction: </strong>The COVID-19 pandemic has necessitated rapid advancements in therapeutic discovery. This study presents an integrated approach combining machine learning (ML) and network pharmacology to identify potential non-covalent inhibitors against pivotal proteins in COVID-19 pathogenesis, specifically B-cell lymphoma 2 (BCL2) and Epidermal Growth Factor Receptor (EGFR).</p><p><strong>Method: </strong>Employing a dataset of 13,107 compounds, ML algorithms such as k-Nearest Neighbors (kNN), Support Vector Machine (SVM), Random Forest (RF), and Naïve Bayes (NB) were utilized for screening and predicting active inhibitors based on molecular features. Molecular docking and molecular dynamics simulations, conducted over a 100 nanosecond period, enhanced the ML-based screening by providing insights into the binding affinities and interaction dynamics with BCL2 and EGFR. Network pharmacology analysis identified these proteins as hub targets within the COVID-19 protein-protein interaction network, highlighting their roles in apoptosis regulation and cellular signaling.</p><p><strong>Results: </strong>The identified inhibitors exhibited strong binding affinities, suggesting potential efficacy in disrupting viral life cycles and impeding disease progression. Comparative analysis with existing literature affirmed the relevance of BCL2 and EGFR in COVID-19 therapy and underscored the novelty of integrating network pharmacology with ML. This multidisciplinary approach establishes a framework for emerging pathogen treatments and advocates for subsequent in vitro and in vivo validation, emphasizing a multi-targeted drug design strategy against viral adaptability.</p><p><strong>Conclusion: </strong>This study's findings are crucial for the ongoing development of therapeutic agents against COVID-19, leveraging computational and network-based strategies.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}