In silico pharmacology最新文献

{"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}

{"title":"Alpha-bisabolol inhibits yeast to hyphal form transition and biofilm development in <i>Candida albicans</i>: in vitro and in silico studies.","authors":"Sayali Chougule, Shivani Patil, Tanjila Gavandi, Sargun Basrani, Ashwini K Jadhav, S Mohan Karuppayil","doi":"10.1007/s40203-025-00335-3","DOIUrl":"10.1007/s40203-025-00335-3","url":null,"abstract":"<p><p>In recent years, there has been growing concern about infections caused by <i>Candida albicans</i>, which pose a significant threat to human health. This intensifies the concern that can be largely attributed to the increasing number of people with compromised immune systems and the emergence of drug-resistant strains. Natural molecules are considered to be good alternatives to synthetic antifungal agents. The present study explored the effectiveness of alpha-bisabolol as an antifungal agent and its mechanism of action against <i>C. albicans</i> ATCC90028. α-bisabolol effectively inhibited various pathogenic traits of <i>C. albicans</i> like, adhesion, yeast to hyphal switching, and development of biofilm at 1 mg/ml, 0.25 mg/ml, and 0.125 mg/ml concentration, respectively. In addition, α-bisabolol demonstrated inhibition of cell cycle propagation at the G1 phase. Ergosterol production in the <i>C. albicans</i> was suppressed by α-bisabolol treatment in a dose-dependent manner. The molecular docking study revealed α-bisabolol has a good binding energy of - 7.11 kcal/mol with 14-α-demethylase enzyme, which is crucial for ergosterol synthesis. Therefore, the cell membrane integrity may be affected by treatment with α-bisabolol. qRT-PCR studies proved that α-bisabolol treatment affects gene expression in <i>C. albicans</i>. In silico binding affinity was also analyzed for <i>RAS1</i>, <i>TUP1</i> and <i>CST20</i> in the signal transduction pathway and exhibited binding affinities for at - 7.7 kcal/mol, - 8.21 kcal/mol, and for - 5.79 kcal/mol respectively. In conclusion, α-bisabolol caused reduced biofilm, ergosterol synthesis along with altered gene expressions in <i>C. albicans</i> with no hemolysis. This study proposed α-bisabolol as an alternative antifungal agent.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"53"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782365","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 dynamics and experimental evaluation of piperine as a potential mTOR inhibitor in colon cancer cells.","authors":"Ifat Jan, Tabasum Ali, Rafat Ali, Nida Jamil Khan, Khurshid Iqbal Andrabi, Ghulam Nabi Bader","doi":"10.1007/s40203-025-00339-z","DOIUrl":"10.1007/s40203-025-00339-z","url":null,"abstract":"<p><p>Piperine, a natural alkaloid found in black pepper (<i>Piper nigrum</i>), has the chemical formula C₁₇H₁₉NO₃ and a molecular weight of 285.34 g/mol. This research investigated its effect on the mTOR protein, which plays a crucial role in cancer development, using molecular docking, dynamic simulations, MTT, and scratch wound assays on the HCT-116 colon cancer cell line. Molecular docking revealed that piperine exhibited a binding affinity of - 8.3 kcal/mol to the mTOR protein, which is significantly comparable to rapamycin's binding affinity of - 8.8 kcal/mol, a well-known mTOR inhibitor. This comparison highlights that piperine demonstrates a substantial ability to interact with the mTOR binding site, making it a potential candidate for further evaluation. Molecular dynamics simulation studies over 100 ns confirmed that piperine remains stable and firmly bound to the mTOR active site, binding in an ATP-competitive mode. MTT assay results revealed that piperine significantly reduced cancer cell viability, with IC50 values of 84.5 ± 0.5 µM at 24 h, 46.3 ± 0.26 µM at 48 h, and 19.73 ± 0.25 µM at 72 h, while the scratch wound assay confirmed its inhibition of cancer cell migration, suggesting potential to suppress metastasis. These findings indicate that piperine is a promising mTOR inhibitor with potential applications in cancer therapy, though further research is needed.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"52"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756789","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":"Identification of phyto-compounds from <i>Mangifera indica</i> as inhibitors of 17β-hydroxysteroid dehydrogenase: a computational approach against prostate cancer.","authors":"Adedotun Olayemi Oluwatuyi, Olusola Olalekan Elekofehinti, Hannah Oluwaseun Popoola, Moses Orimoloye Akinjiyan, Idayat Oyinkansola Kehinde, Ifeoluwa Racheal Adetoyi, Olufemi Adebisi Akinola, Folasade O Ayodeji, Olabimpe Omolola Apeji, Adeola Victor Kolawole, Akinola Oluwadamilola Dorcas, Alonge Sunday Ayodeji","doi":"10.1007/s40203-025-00332-6","DOIUrl":"10.1007/s40203-025-00332-6","url":null,"abstract":"<p><p>Prostate cancer (PrCa) is a serious health concern for the affected people and, there is an increasing demand for a viable therapy that can address the limitations of current treatments with minimal or no adverse effects. This study aims to evaluate phytocompounds extracts of <i>Mangifera indica</i> as a potential therapy development for prostate cancer. Herein, molecular docking, QSAR, molecular mechanics/generalized born surface area (MM/GBSA) estimation, ADME screening, and molecular dynamics (MD) simulation were performed using the Schrodinger suite to identify 17β-hydroxysteroid dehydrogenase antagonist from <i>Mangifera indica</i>. The results showed that fisetin (-11.669), riboflavin (-10.918), quercetin (-10.843), gallic acid 6-phenylhexyl ester (-10.817), cianidanol (-10.608), (-)-epicatechin (-10.603), ellagic acid (-10.522), Butin (-10.124) in kcal/mol were predicted to possess greater inhibitory activities against the protein target based on their high binding energies and remarkable stability compared to the standard drug, docetaxel (-7.374 kcal/mol). Fisetin (-718.37), and riboflavin (-722.37) also have better induce fit score than docetaxel (-714.02) in kcal/mol with better pharmacokinetics profile compared to the standard drug.MD simulation over 100 ns predicts that Fisetin forms stable interactions with vital residues at the catalytic site of the protein. The observations from this study predict fisetin as a putative antagonist of 17β-hydroxysteroid dehydrogenase and should be experimentally verified as a lead compound for prostate cancer therapy.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"50"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756785","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":"Computational investigation of antiviral peptide interactions with Mpox DNA polymerase.","authors":"Harshit Tiwari, Ashal Ilyas, Pankaj Kumar Rai, Shashank Upadhyay, Subhomoi Borkotoky","doi":"10.1007/s40203-025-00342-4","DOIUrl":"10.1007/s40203-025-00342-4","url":null,"abstract":"<p><p>The Mpox DNA polymerase (DNA pol) plays a crucial role in the viral replication process, making it an ideal target for antiviral therapies. It facilitates the synthetic process of viral DNA, which is an integral stage in the life of a virus. The inhibition of the operation of Mpox DNA pol would interfere with the multiplication of the virus and help manage the disease. Peptides have emerged as a possible therapeutic alternative against viruses due to their distinct characteristics. Peptides have broad-spectrum antiviral activity, being effective against a variety of viruses. Using computational techniques, we attempted to explore the molecular details of the interaction between antiviral peptides and Mpox DNA pol. Two databases of antiviral peptides were screened in this study. This study used molecular docking, followed by molecular dynamics (MD) simulation and post-simulation binding energy predictions. From the 19 selected peptides with activity against DNA polymerases, two peptides-DRAVPe01393 and DRAVPe01399-were identified as particularly promising candidates. These peptides exhibited stable interactions with Mpox DNA pol and demonstrated good cell penetration potential as evident from the MD simulation studies. Notably, the peptides DRAVPe01399 and DRAVPe01393 have a better binding affinity of - 60.86 kcal/mol and - 47.92 kcal/mol respectively than the control ligand Cidofovir diphosphate (- 10.79 kcal/mol). These findings could lead to the development of innovative antiviral treatments to prevent monkeypox, helping global efforts to battle this emerging infectious disease.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"49"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756579","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}