In silico pharmacology最新文献

{"title":"Network pharmacology and molecular docking of <i>Fraxinus floribunda</i>: validating ethnomedicinal applications in T2DM.","authors":"Arunika Subba, Rohit Rai, Ranjan Kumar Prasad, Isaac Shilall, Aditya Moktan Tamang","doi":"10.1007/s40203-025-00348-y","DOIUrl":"10.1007/s40203-025-00348-y","url":null,"abstract":"<p><p>The current study investigates the network pharmacology, molecular docking, and molecular dynamics (MD) simulation of <i>Fraxinus floribunda</i> Wall. (Oleaceae) to validate its ethnomedicinal applications in Type 2 Diabetes Mellitus (T2DM). Five major bioactive compounds were identified using IMPPAT and TCMSP databases, based on pharmacokinetic properties (OB > 20%, DL > 0.18). Target genes for these compounds were predicted using Swiss Target Prediction, focusing on human targets with a high confidence score. A protein-protein interaction (PPI) network was constructed using the STRING database, revealing significant interactions among 143 nodes and 1300 edges. Molecular docking analysis revealed strong binding affinities of quercetin (- 10.4 kcal/mol), tamarixetin (- 10.4 kcal/mol), and isorhamnetin (- 9.5 kcal/mol) with MMP9, forming hydrogen bonds with key residues such as ALA189, GLN227, and TYR248. Molecular dynamics (MD) simulations confirmed the stability of the quercetin-MMP9 and tamarixetin-MMP9 complexes, with low RMSD values (~ 0.151 nm). Further, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations revealed favorable binding free energies, with quercetin exhibiting the highest binding affinity (- 6.82 kJ/mol), followed by tamarixetin (4.60 kJ/mol) and isorhamnetin (10.16 kJ/mol), reinforcing their potential role as MMP9 inhibitors. The findings highlight the potential of <i>F. floribunda's</i> bioactive compounds in managing T2DM, bridging traditional medicinal knowledge with modern computational tools to accelerate drug discovery and development. This integrative approach underscores the multifaceted pharmacological properties of <i>F. floribunda</i>, including antioxidant, anti-inflammatory, and potentially anti-obesity effects, aligning with broader health benefits beyond diabetes management. Further research and clinical validation are warranted to harness these natural compounds effectively for therapeutic development against T2DM and related metabolic disorders.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00348-y.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"60"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variants in the <i>LRP5</i> gene associated with gain and loss of bone mineral density.","authors":"Daphany Marah Gorges, Fabíola Branco Filippin-Monteiro","doi":"10.1007/s40203-025-00341-5","DOIUrl":"10.1007/s40203-025-00341-5","url":null,"abstract":"<p><p>The low-density lipoprotein receptor-related protein 5 (LRP5) plays a pivotal role in bone formation, influencing the proliferation and differentiation of osteoblasts and thereby impacting overall bone mass. Genetic variations stemming from non-synonymous single nucleotide polymorphisms (nsSNPs) within the LRP5 gene can lead to either enhanced or diminished function of the resultant protein, culminating in distinct phenotypic expressions such as osteoporosis-pseudoglioma syndrome (OPPG) and high bone mass (HBM). Through in silico analysis of 17 identified nsSNPs, it was observed that 14 of these variants induced damage at highly conserved sites, resulting in the destabilization of both protein function and structure. Notably, the functional alteration, be it a gain or loss, is primarily dictated by the interaction between the molecule and LRP5, rather than the specific amino acid substitution. This research offers an identification of detrimental nsSNPs within the LRP5 protein and serves as a foundation for population-based investigations into the phenotypic repercussions on a broader scale.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"61"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the neuroprotective effects of strawberry extract against diesel soot-induced motor dysfunction in Drosophila: an in-vivo and in-silico study.","authors":"Adithi Gopadi Ravindranath, Ananya Muralidhar, Nidhi Narayan Gambhir, Jhinuk Chatterjee","doi":"10.1007/s40203-025-00344-2","DOIUrl":"10.1007/s40203-025-00344-2","url":null,"abstract":"<p><p>Environmental pollutants including diesel soot, have been known to contribute to neurological disorders. Previous studies highlight the neuroprotective effects of strawberry-derived compounds. This work explores the impacts of diesel soot and strawberry extract in movement-related disorders. <i>In-silico</i> analysis assessed compounds from HPLC/GCMS in the literature of soot and strawberry extract for ADME properties and blood-brain barrier permeability, selecting six compounds and four motor function-related proteins (SOD1, TARDBP, FUS, MAPT) with <i>D. melanogaster</i> orthologs. Homology modeling generated protein structures, molecular docking assessed binding affinities. MLSD examined combined interactions, with RMSD validating accuracy. Docking scores matched neuroprotective controls (quercetin, resveratrol), while differed for negative control (formaldehyde). Phenanthrene and anthocyanin strongly bound to FUS (- 7.60 ± 0.26 kcal/mol, - 7.1 ± 0.26 kcal/mol) and cocoon (- 6.5 ± 0.39 kcal/mol, - 7.23 ± 0.45 kcal/mol). MLSD yielded - 3.00 ± 0.24 kcal/mol and - 3.12 ± 0.11 kcal/mol respectively. In-vivo assays in <i>D. melanogaster</i> exhibited soot impaired movement (p = 0.0006), while strawberry improved it (p = 0.0003) with partial recovery in combined exposure (p = 0.0003). Strawberry enhanced cold stress recovery (p = 0.0048), climbing (p < 0.0001), and vortex recovery (p = 0.0003). One-way ANOVA confirmed significant effects on crawling in males (<i>F (9,20)</i> = <i>37.67, p</i> < <i>0.0001, η</i> ^<i>2</i>  = <i>0.53</i>) and female flies (<i>F (9,20)</i> = <i>70.10, p</i> < <i>0.0001</i>), with normality confirmed by Shapiro-Wilk test (p > 0.05). Toxicant exposure accelerated mortality, while strawberry improved thermotolerance. Combined exposure provided partial protection with minor sex differences. Findings highlight strawberries' neuroprotective role in counteracting diesel soot toxicity, even under combined exposure.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00344-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"58"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Docking and dynamic simulation analysis of flavonoid derivatives as COX-2 inhibitors.","authors":"Pasula Janakiramulu, Estari Mamidala","doi":"10.1007/s40203-025-00349-x","DOIUrl":"10.1007/s40203-025-00349-x","url":null,"abstract":"<p><strong>Abstract: </strong>Cyclooxygenase-2 (COX-2) is a key enzyme involved in inflammation and tumor progression, playing a significant role in the development of various cancers, including colorectal, breast, lung, and prostate cancers. In this study, molecular docking and molecular dynamics (MD) simulations were conducted to evaluate the binding potential and stability of flavonoid compounds as potential COX-2 inhibitors. A total of 36 flavonoid compounds were selected based on pharmacokinetic properties and subjected to molecular docking analysis. Binding affinity calculations revealed that several flavonoids exhibited strong interactions with COX-2, with Cudraflavone A showing the highest binding affinity of - 10.19 kcal/mol, surpassing the standard inhibitor Rofecoxib (- 9.4 kcal/mol). Key interactions were identified with critical active site residues, including Tyr130, Glu465, and Arg44, through hydrogen bonding and hydrophobic interactions. To further assess the stability of the COX-2-flavonoid complex, molecular dynamics simulations were performed using GROMACS. Root-mean-square deviation (RMSD) analysis demonstrated that the COX-2-Cudraflavone A complex exhibited greater structural stability compared to the unbound enzyme. Root-mean-square fluctuation (RMSF) analysis indicated reduced flexibility in key regions of the enzyme upon ligand binding, reinforcing its stabilizing effect. Additionally, the radius of gyration (Rg) analysis confirmed that the complex maintained a more compact conformation, suggesting enhanced structural integrity. These findings suggest that Cudraflavone A is a promising candidate for COX-2 inhibition, exhibiting superior binding affinity and stabilizing effects. This study provides valuable insights into the potential development of flavonoid-based COX-2 inhibitors for cancer and anti-inflammatory therapeutics.</p><p><strong>Graphic abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00349-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"59"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the anticancer properties of starter culture of Tripura: an in-silico study on non-small cell lung cancer.","authors":"Rahel Debbarma, Sony Kumari, Shiva Aley Acharjee, Pranjal Bharali","doi":"10.1007/s40203-025-00354-0","DOIUrl":"10.1007/s40203-025-00354-0","url":null,"abstract":"<p><p>This study investigates the anticancer properties of the starter culture from Tripura using in-silico analysis focused on non-small cell lung cancer (NSCLC). Proximate analysis reveals the starter culture's suitability for fermentation, with a moisture content of 26.6 ± 0.5%, ash content of 1.52 ± 1.9%, carbohydrate content of 30 ± 0.5 mg/ml, crude protein content of 35.12 ± 0.4 µg/ml, and total soluble sugar content of 29 ± 0.3, which collectively ensure optimal microbial stability and activity. Antioxidant analysis demonstrated moderate capacity, with an IC₅₀ value of 48.5 µg/mL and significant flavonoid content (15 ± 0.23 mg quercetin equivalent/g%), enhancing the nutritional and sensory qualities of rice beer. GC-MS analysis identified over twenty bioactive compounds, including trans-13-octadecenoic acid, sitostenone, Ergosta-4,6,8(14),22-tetraen-3-one, N-Hexadecenoic acid, and 2-Pentadecanone. These compounds exhibit diverse bioactivities such as antioxidant, anticancer, and antibacterial properties. Molecular docking studies showed that Ergosta-4,6,8(14),22-tetraen-3-one had the highest binding affinity for the ErbB2 (HER-2) receptor, with a binding energy of - 8.5 kcal/mol, suggesting significant potential to inhibit lung cancer cell proliferation. Drug-likeness assessment based on Lipinski's Rule of Five indicated favorable properties for oral bioavailability, although some compounds exceeded the MolLogP threshold. Pharmacokinetic studies highlighted high gastrointestinal absorption and blood-brain barrier permeability for trans-13-octadecenoic acid, despite potential challenges related to drug metabolism inhibition. This work highlights the integration of traditional knowledge with modern scientific approaches for the development of innovative anticancer drugs, underscoring the importance of traditional starter cultures in the production of rice beer with enhanced health benefits and therapeutic potentials.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"64"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the mechanism of core prescription in primary liver cancer: integrative analysis through data mining, network pharmacology, and molecular simulation.","authors":"Qingsi Zhao, Gaoyue Dong, Xinyue Zhang, Xing Gao, Hongyu Li, Zhongyuan Guo, Leilei Gong, Hong Yang","doi":"10.1007/s40203-025-00352-2","DOIUrl":"10.1007/s40203-025-00352-2","url":null,"abstract":"<p><p>This study aims to identify core Traditional Chinese Medicine compound prescriptions (TCM CPs) for Primary Liver Cancer (PLC) and their underlying mechanisms. A comprehensive search was conducted using China National Knowledge Infrastructure (CNKI) and the Chinese Medical Code V5.0, identifying 151 TCM CPs. Medication frequency and association rules were analyzed with TCMICS V3.0, while active compounds were identified via TCMSP and TCMIP V2.0. Targets were predicted using Swiss Target Prediction, and disease targets from DisGeNET, OMIM, and GeneCards were cross-referenced. A protein-protein interaction (PPI) network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using DAVID. In the process of studying active compounds, an orthogonal experiment was carried out on the extraction process of relevant herbs. The results of the orthogonal experiment and range analysis showed that for the extraction rate of the extract and the content of paeoniflorin, the decoction cycles had the most significant impact, followed by soaking time and water volume. The optimal extraction conditions were determined as soaking time of 30 min, water volume of tenfold, and 3 decoction cycles. Under these conditions, the extract yield reached 42.49%, and the paeoniflorin content was 73.60 mg/25.02 g crude herb (equivalent to 2.94 mg/g). ANOVA analysis further confirmed the significance of these factors. The results revealed 109 common targets between TCM component targets and disease targets, with key targets including STAT3, SRC, AKT1, HRAS, and PIK3CA. Molecular docking showed strong binding affinities of paeoniflorin and 3,5,6,7-tetramethoxy-2-(3,4,5-trimethoxyphenyl) chromone to PLC targets, with ADME predictions favoring paeoniflorin. Furthermore, Molecular Dynamics (MD) simulations revealed that paeoniflorin maintains stable binding to the target proteins, demonstrating promising conformational stability. The CCK-8 assay demonstrated that the core TCM CP exerted a dose-dependent inhibitory effect on HepG2 cells. After 24 h of intervention, the IC₅₀ values of paeoniflorin and the TCM CP on HepG2 cells were 17.58 μg/mL and 120.5 μg/mL, respectively, which confirmed their anti-proliferative activity against PLC. This study identifies key active compounds and investigates their roles in modulating the Ras/Raf/MEK/ERK, AKT/NF-κB, and JAK-STAT signaling pathways, offering valuable insights into the therapeutic potential of TCM for PLC treatment.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00352-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"63"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABAergic antidepressant effect of daidzin: in vivo approach with in silico receptor binding affinities.","authors":"Md Torequl Islam, Md Showkot Akbor, Md Shimul Bhuia, Rubel Hasan, Raihan Chowdhury, Md Amirul Islam, Md Saifuzzaman","doi":"10.1007/s40203-025-00357-x","DOIUrl":"10.1007/s40203-025-00357-x","url":null,"abstract":"<p><p>Daidzin (DZN: 7-(β-D-Glucopyranosyloxy)-4-hydroxyisoflavone) is a soy plant-derived isoflavone. It has diverse biological activities, including nephroprotective effects. To date, its anxiolytic, memory-enhancing, and antiepileptic properties have been discovered. However, its antidepressant activity has not yet been investigated.This study aimed to investigate DZN's antidepressant activity through animal and in silico studies. Male <i>Swiss</i> albino mice were randomly divided into nine groups consisting of control (vehicle), DZN 5, 10, and 20mg/kg, diazepam (GABA_A agonist), flumazenil (GABA_A antagonist), and a combination of DZN-10 with diazepam and/or flumazenil. Additionally, in silico studies were also performed to understand the possible molecular mechanisms behind this neurological activity. Findings suggest that DZN dose-dependently and significantly (<i>p</i> < 0.05) enhanced immobility time (IMT) in animals. DZN-10 also increased diazepam's effects significantly (<i>p</i> < 0.05), possibly by raising its IMT values. However, DZN significantly (<i>p</i> < 0.05) declined flumazenil's effect in their combination. In silico findings suggest that DZN has a strong binding affinity against GABA_A receptor subtypes. We suppose DZN exerts its antidepressant effect, possibly by interacting with GABA_A receptors. It exerts a synergistic effect with the GABA agonist drug diazepam. Further studies are required to determine the exact molecular mechanism behind this neurological activity.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"57"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of acyl-homoserine-lactone synthase in <i>Pseudomonas aeruginosa</i> biofilms by 7-O-methyl-aromadendrin by using molecular docking and molecular dynamics simulation.","authors":"Mohammad Jalal Nazari, Mohammad Tariq Anwary, Khanbaba Ghazanfar, Mohammad Edris Amiri, Sayed Yahya Hafid, Mohammad Jawad Jawad, Sayed Hussain Mosawi","doi":"10.1007/s40203-025-00350-4","DOIUrl":"10.1007/s40203-025-00350-4","url":null,"abstract":"<p><p>This study investigates the potential of 7-O-methyl aromadendrin (7-OMA), a naturally occurring flavonoid-glycoside, as an inhibitor of acyl-homoserine-lactone (AHL) synthase in <i>Pseudomonas aeruginosa</i>, a key enzyme in quorum sensing and biofilm formation. Using molecular docking and molecular dynamics simulations, we evaluated the binding interactions and inhibitory effects of 7-OMA on AHL synthase. Molecular docking revealed a suitable binding affinity (-6.66 kcal/mol) between 7-OMA and the enzyme, with interactions at critical active site residues. Molecular dynamics simulations demonstrated that 7-OMA stabilizes the enzyme through hydrogen bonds and van der Waals interactions while enhancing its structural flexibility. The average RMSD of AHL synthase increased slightly in the presence of 7-OMA, indicating partial instability of the enzyme. Additionally, the average Rg value increased, suggesting that 7-OMA may expand the enzyme structure or reduce its compactness. MM-PBSA analysis confirmed the strength of these interactions, with favorable van der Waals and electrostatic contributions to the binding energy. These results suggest that 7-OMA disrupts the structural dynamics of AHL synthase, potentially inhibiting biofilm formation and reducing the virulence of <i>Pseudomonas aeruginosa</i>. The findings highlight the therapeutic potential of 7-OMA as a novel inhibitor of AHL synthase, offering a promising strategy to combat biofilm-associated infections. Future studies should focus on evaluating the bioavailability, in vivo efficacy, and clinical applicability of 7-OMA, as well as its broader activity against other multidrug-resistant pathogens.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"56"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of potential inhibitors against chikungunya envelope: an in-silico clue.","authors":"Aparna Chaudhuri, Bidyut Bandyopadhyay, Buddhadev Mondal, Aniket Sarkar, Sabyasachi Ghosh, Anindya Sundar Panja","doi":"10.1007/s40203-025-00351-3","DOIUrl":"10.1007/s40203-025-00351-3","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is a mosquito-borne virus which causes chikungunya disease. Two biological vectors <i>Aedes aegypti</i> and <i>Aedes albopictus</i> transmit CHIKV to the victim body. According to the report of the European Centre for Disease Prevention and Control, epidemics of chikungunya disease existed in 2024 over America, Africa, Europe and Asia. Although 50% CHIKV infected person show chronic clinical symptoms and several troubles associated with chikungunya, still there are no effective vaccines or medications on market. So availability of another CHIKV inhibiting materials and mechanisms are necessary. For this purpose recently plant-derived bioactive compounds with antiviral properties are used to inhibit chikungunya infection. In this present research work 69 CHIKV inhibiting active compounds were chosen for ADMET analysis. Drug likeness of active compounds was also analyzed based on Lipinski's rule of five. Based on the drug likeness, active compounds (Baicalein, Epicatechin, Genistein, Quercetin, Resveratrol<b>)</b> were finally screened for molecular docking with CHIKV envelope proteins using Auto Dock program. Among the five active compounds, Genistein showed highest binding energy for both E1 (ΔG = - 8.3 kcal/mol) and E2 (ΔG = - 7.1 kcal/mol). Molecular dynamics simulations signify that Genistein forms a stable complex with the CHIKV E1 and E2 proteins over a 50 ns period with a significant number of hydrogen bonds. So this present study concluded that Genistein will act as potent CHIKV E1 and E2 inhibiting active compounds. To evaluate efficiency or inhibiting capacity of finally selected Genistein against CHIKV, in vivo and in vitro validation should be conducted.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00351-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"55"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthelmintic activity of <i>Calotropis gigantea</i>: in silico investigation on novel target site nematode kinases.","authors":"Velan Gopalakrishnan, Thiruvenkadam Mahendiran","doi":"10.1007/s40203-025-00331-7","DOIUrl":"10.1007/s40203-025-00331-7","url":null,"abstract":"<p><p>Over one billion peoples are currently infected with a parasitic nematode, particularly in tropical regions. Helminthiasis is a medical condition characterized by an infection of parasitic worms in the human body. <i>Calotropis gigantea</i> Linn. Belongs to the Asclepiadaceae family, commonly known as \"Gaint milkweed\" or \"Crown flower\" and recognized as a traditional medicinal plant. In this study, anthelminthic potential of <i>Calotropis gigantea</i> phytoconstituents were determined. Nematode kinases EGFR, MEK1, and PLK1 have diverged from their vertebrate counterparts in their drug-binding pockets. The development of novel anthelmintics targets Kinases that hold potential as targets. This pipeline revealed three potential anthelmintic targets that include epidermal growth factor tyrosine kinase transmembrane receptor [EGFR], the Mitogen-activate protein kinase [MEK1], and polo-like kinase [PLK1]. The software used in the in silico study investigation is the pyRx virtual screening tool, Biovia Discovery Studio, mol-inspiration, and RCSB [Protein Data Bank (PDB)]. The various phytoconstituents of <i>Calotropis gigantea</i> were docked Stigmasterol, beta-sitosterol, Desmosterol, alpha-amyrin, asclepin, and others showed high binding energies in EGFR, MEK1, and PLK1 receptors. This investigational study research highlights the potential of phytoconstituents from <i>Calotropis gigantea</i> as anthelmintic activity.</p><p><strong>Graphic abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"54"},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}