In silico pharmacology最新文献

{"title":"Targeting cardiotoxicity: the potential of <i>Annona squamosa</i> L. in doxorubicin therapy.","authors":"Kshitij A Lele, Priyanka P Patil, Sneha V Kakade, Naveen R Maledavar, Shriram D Ranade, Shankar G Alegaon, Prakash R Biradar, Nayeem A Khatib","doi":"10.1007/s40203-025-00333-5","DOIUrl":"10.1007/s40203-025-00333-5","url":null,"abstract":"<p><p>Doxorubicin, a potent anthracycline used in chemotherapy, is limited by dose-dependent cardiotoxicity, leading to irreversible heart damage and heart failure. Common symptoms include fatigue, dyspnea, lower limb edema, hypotension, tachycardia, and transient arrhythmias. <i>Annona squamosa</i> L. (AS), traditionally used in medicine, was investigated for its cardioprotective action against doxorubicin-induced cardiotoxicity through computational studies. Phytocompounds were identified using literature reviews, Dr. Duke's, IMPPAT, and PubChem databases. Targets associated with Doxorubicin induced cardiotoxicity were accessed from GeneCards, and protein-protein interactions were analyzed using the STRING database. Cytoscape was used for network visualization, revealing 18 bioactives targeting 67 proteins across 14 pathways. PIK3R1 emerged as a key target with the highest interaction count among 767 targets. Molecular docking showed that the PIK3R1-Rutin complex had the lowest binding energy (- 11.873 kcal/mol), and a 100 ns molecular dynamics (MD) simulation confirmed its stability. LC-MS analysis of the crude extract indicated the presence of bioactives. In vitro antioxidant activity of AS, assessed using the DPPH assay, showed significant radical scavenging activity, correlating with the high total phenol (TPC) and total flavonoid content (TFC) detected. This integrated approach highlights AS's potential in mitigating doxorubicin-induced cardiotoxicity.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00333-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"47"},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665780","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":"Natural compounds as therapeutic candidates for spinocerebellar ataxia type 1: a computational approach.","authors":"Surbhi Singh, Suchitra Singh, Deepika Joshi, C Mohanty, Royana Singh","doi":"10.1007/s40203-025-00308-6","DOIUrl":"10.1007/s40203-025-00308-6","url":null,"abstract":"<p><p>Spinocerebellar Ataxia Type 1 (SCA1) is a progressive neurodegenerative disorder caused by the expansion and aggregation of polyglutamine (polyQ) in the Ataxin-1 (ATXN1) protein, leading to severe neuronal dysfunction. Currently, only symptomatic treatments are available, highlighting the requirement for disease-modifying therapies. This study employed a detailed in silico approach to identify potential neuroprotective natural compounds targeting the Ataxin-1 protein implicated in SCA1. The three-dimensional structure of Ataxin-1 was retrieved, validated, and optimized to achieve a stable structural model. Validation using a Ramachandran plot indicated that 77% of the residues were in favored regions, confirming the reliability of the protein structure. Active site residues were identified using CASTp, and receptor grids were generated for molecular docking studies. A library of 50 natural compounds was screened, among which 21 satisfied Lipinski's rule of five. Molecular docking using PyRx and AutoDock 4.2 identified Withanolide A as the top candidate, exhibiting the highest binding affinity (- 10.14 kcal/mol) and forming four hydrogen bonds with key active site residues. The top six ligands were further assessed for ADMET properties, with Withanolide A showing optimal drug-likeness, high gastrointestinal and blood-brain absorption, and non-toxic profiles. Molecular dynamics simulations over 200 ns demonstrated the stability of the Ataxin-1-Withanolide A complex, supported by RMSD, RMSF, RoG, and SASA analyses. PCA revealed reduced conformational flexibility, indicating enhanced structural stability of the ligand-bound complex. Additionally, MM-PBSA analysis confirmed that Van der Waals interactions were the primary stabilizing forces, complemented by electrostatic contributions. This integrated computational approach highlights the therapeutic potential of Withanolide A as a neuroprotective agent for SCA1, providing a base for future experimental validation and drug development.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"46"},"PeriodicalIF":0.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652794","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":"Deciphering the the molecular mechanism of aloe-emodin in managing type II diabetes mellitus using network pharmacology, molecular docking, and molecular dynamics simulation approaches.","authors":"Samuel Baker Obakiro, Kenedy Kiyimba, Yahaya Gavamukulya, Richard Maseruka, Catherine Nabitandikwa, Ronald Kibuuka, Jalia Lulenzi, Tonny Wotoyitide Lukwago, Mercy Chebijira, Moses Opio, Edeya Sharon Tracy, Dan Kibuule, Richard Owor Oriko, Paul Waako, Angela Makaye, Daniel M Shadrack, Moses Andima","doi":"10.1007/s40203-025-00337-1","DOIUrl":"10.1007/s40203-025-00337-1","url":null,"abstract":"<p><p>Aloe-emodin (AE) has drawn interest due to its potential activity against type II diabetes mellitus (T2DM). However, the mechanisms underlying its antidiabetic activity are not well explored. Using network pharmacology, molecular docking and molecular dynamics simulation studies, we investigated its molecular mechanisms in the management of T2DM. Potential target genes of AE were predicted using the Swiss Target Prediction (http://www.swisstargetprediction.ch/) database. The GeneCards, OMIM and DisGeNET databases were used to compile a comprehensive list of genes associated with T2DM. A compound-disease-target network was constructed, and protein-protein interaction networks were analysed to identify hub genes. Finally, molecular docking and interaction analysis between AE and the identified proteins were performed using AutoDock tools. Investigation of AE targets and genes associated with T2DM identified 32 overlapping genes. Gene ontology studies revealed that AE may exert its anti-diabetic effects by modulating glucose metabolism and enhancing cellular response to glucose. Furthermore, KEGG pathway analysis suggested that AE influences these processes by targeting pathways related to apoptosis, insulin resistance, and T2DM signaling. The core target proteins identified were TNF, ALB, TP53, PPARG, BCL2, CASP3, and EGFR. AE interaction with each of these proteins exhibited a binding energy of > - 5 kcal/mol, with TNF showing the lowest binding energy (- 7.75 kcal/mol). Molecular dynamics simulation further validated the molecular docking results with TNF and EGFR exhibiting a strong affinity for AE and forming stable interactions. AE exerts its antidiabetic activity through multiple mechanisms, with the most significant being the amelioration of pancreatic β-cell apoptosis by binding to and inhibiting the actions of TNFα. Further cellular and molecular studies are needed to validate these findings.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00337-1.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"45"},"PeriodicalIF":0.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652864","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":"Plant-derived Bisphenol C is a drug candidate against <i>Nipah henipavirus</i> infection: an in-vitro and in-silico study of <i>Pouzolzia zeylanica</i> (L.) Benn.","authors":"Mahadi Hasan, Md Tariquzzaman, Md Raysul Islam, Tasmina Ferdous Susmi, Md Shahedur Rahman, Md Sifat Rahi","doi":"10.1007/s40203-025-00328-2","DOIUrl":"https://doi.org/10.1007/s40203-025-00328-2","url":null,"abstract":"<p><p><i>Pouzolzia zeylanica</i> (PZ) is a widely distributed medicinal herb throughout Bangladesh, especially in tribal regions. The present study focused on evaluating the bioactivity like antioxidant, cytotoxicity, anti-hemolytic activity through in-vitro assessment and predicted potential antiviral compounds against Nipah virus employing in-silico approaches from stem extract of <i>P. zeylanica</i>. The bioactivities of stem extract showed potent antioxidant and anti-hemolytic activity. Comparatively, its cytotoxicity, with an IC₅₀ of 123.786 ± 1.328 µg/ml, suggests moderate toxicity, making it a potential source for therapeutics. Through GCMS analysis, 17 compounds were identified from the stem extract. On the other hand, the potent ligand targeting attachment glycoprotein, the key factor during the host-pathogen attachment and disease (encephalitis) progression, of the Nipah virus (NiV-G) was predicted through in-silico approaches employing ADMET analysis, molecular docking, quantum mechanics (QM) and molecular dynamic simulation (MDS). With a docking score of - 7.4kCal/mol in molecular docking analysis between phytochemicals and NiV-G, Bisphenol-C (CID6620) has been identified as a potent ligand among the phytochemicals present in PZ stem extract. The QM analysis suggests kinetic stability with better chemical reactivity and the docked complex was found stable in MDS for 100 ns. Based on all those evaluations, the compound could be considered a potent ligand for NiV-G and indicates a promising antiviral drug candidate.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00328-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"43"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652804","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":"In silico docking and ADMET studies on clinical targets for type 2 diabetes correlated to in vitro inhibition of pancreatic alpha-amylase and alpha-glucosidase by rutin, caffeic acid, p-coumaric acid, and vanillin.","authors":"Jamie McMillan, Megan Jean Bester, Zeno Apostolides","doi":"10.1007/s40203-025-00324-6","DOIUrl":"https://doi.org/10.1007/s40203-025-00324-6","url":null,"abstract":"<p><p>Inhibition of pancreatic alpha-amylase and alpha-glucosidase is a common strategy to manage type 2 diabetes. This study focuses on the ability of compounds present in commercially available herbs and spices to inhibit pancreatic alpha-amylase and alpha-glucosidase. In silico molecular docking was performed to evaluate the binding affinity of the compounds present in herbs and spices. Molecular dynamics was performed with acarbose and rutin which had the best docking scores for pancreatic alpha-amylase and alpha-glucosidase. Six compounds (rutin, caffeic acid, p-coumaric acid, vanillin, ethyl gallate, and oxalic acid) with a range of docking scores were subjected to in vitro enzyme kinetic studies using pancreatic alpha-amylase and alpha-glucosidase biochemical assays. Acarbose, a prescribed alpha-amylase and alpha-glucosidase inhibitor, was used as a positive control. Ligands that interacted strongly with the amino acids at a particular site, were conformationally stable and had good docking scores. There was a correlation between the in silico and in vitro binding affinity. Caffeic acid, vanillin, ethyl gallate, and p-coumaric acid had inhibition constant (K_i) values that were not significantly different (<i>p</i> > 0.05) from the K_i of acarbose for pancreatic alpha-amylase. Rutin, caffeic acid, vanillin, and p-coumaric acid had K_i values that were not significantly different (<i>p</i> ˃ 0.05) from the K_i of acarbose for alpha-glucosidase. The cell viability of these compounds was assessed with the sulforhodamine B (SRB) assay in Caco2 cells. Caffeic acid, p-coumaric acid, rutin, and vanillin had Caco2 IC₅₀ values that were not significantly different (<i>p</i> ˃ 0.05) from that of acarbose. The evaluated compounds present in herbs and spices can potentially reduce hyperglycemia associated with type 2 diabetes. Herbs and spices with high levels of these compounds were identified and these were common verbena, sweet basil, tarragon, pepper, parsley, sorrel, and vanilla. These herbs and spices may reduce the required dose of prescription drugs, such as acarbose, thereby reducing costs and drug-associated side effects.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00324-6.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"42"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652929","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, pharmacological profiling, and MD simulations of glycolytic inhibitors targeting novel SARS CoV-2 main protease and spike protein.","authors":"Nikhil Kumar, Chandraprakash Gond, Jai Deo Singh, Anupama Datta","doi":"10.1007/s40203-025-00336-2","DOIUrl":"https://doi.org/10.1007/s40203-025-00336-2","url":null,"abstract":"<p><strong>Abstract: </strong>Coronavirus infection (COVID-19), designated a global health emergency by the World Health Organization in 2020, continues to spur the search for effective therapeutics. The causative agent, SARS-CoV-2, depends on viral proteins and host metabolic reprogramming for replication. This study explores the potential of glycolytic inhibitors as dual-action agents against SARS-CoV-2, explicitly targeting the main protease and the spike protein due to their critical roles in viral replication and cellular entry. These inhibitors disrupt the activity of viral proteins and host cell glycolysis, thereby preventing viral propagation. Through a combination of virtual screening, molecular docking, and molecular dynamics simulations, fluoro-deoxy-glucose folate (FDGF) and N-(2-fluoro-3-(6-O-glucosylpropyl-azomycin)) were identified as potent candidates. The docking results showed strong binding affinities, with scores of -8.6 and -7.1 kcal/mol for main protease and -9.9 and - 7.5 kcal/mol for spike receptor-binding domain bound to ACE2. Further molecular dynamic simulations confirmed the stability of the FDGF complexes, with RMSD fluctuations consistently remained within 1.6-2.9 Å over a 100 ns trajectory. Additionally, MM-GBSA binding free energy calculations revealed favorable binding energies, underscoring the stability and potential efficacy of these compounds. Overall, the findings suggest that FDGF and N-(2-fluoro-3-(6-O-glucosylpropyl-azomycin)) show promise as SARS-CoV-2 therapeutics, warranting further in vitro and in vivo validation to confirm their antiviral potential.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00336-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"44"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652519","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 novel phytochemicals as α-synuclein aggregation inhibitors in the context of Parkinson's disease therapy: an in-silico approach.","authors":"Garima Gupta, Deepika Joshi, Gopeshwar Narayan, Sameer Sharma","doi":"10.1007/s40203-025-00330-8","DOIUrl":"10.1007/s40203-025-00330-8","url":null,"abstract":"<p><p>The misfolding and aggregation of alpha-synuclein play a pivotal role in the pathogenesis of Parkinson's disease (PD), contributing to neuronal dysfunction, the formation of Lewy bodies, and the manifestation of motor symptoms characteristic of PD. Understanding these molecular mechanisms is imperative for advancing therapeutic strategies for this neurodegenerative disorder. Current treatment modalities primarily involve dopamine replacement drugs, which fail to halt or slow disease progression. This study employs in-silico methods, including molecular docking and molecular dynamics simulations, to comprehensively evaluate naturally derived phytochemicals (<i>n</i> = 875) with neuroprotective or therapeutic potential in PD. Among these compounds, Crebanine exhibited the least binding energy at 13.7 kcal/mol, while Alpinetin showed -  3.2 kcal/mol. The RMSD values remained consistent after approximately 60 ns and 40 ns for Crebanine and Alpinetin, respectively, indicating stable predicted models. These findings underscore the potential of phytocompounds as candidates for PD therapeutics and warrant further in vitro and in vivo investigations to validate their efficacy. This approach represents a promising avenue for developing novel treatments that target the underlying molecular mechanisms of PD.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"37"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588990","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":"Evaluation of various bioactive molecules for their gp120-CD4 binding inhibitory properties by in-silico molecular docking and dynamic studies.","authors":"Honey Tank, Niketan Deshmukh","doi":"10.1007/s40203-025-00327-3","DOIUrl":"10.1007/s40203-025-00327-3","url":null,"abstract":"<p><p>Acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), remains a significant global health challenge, affecting over 38.4 million individuals worldwide according to the World Health Organization (WHO). The high mutation rate of HIV complicates the effectiveness of conventional antiviral drugs, necessitating novel therapeutic approaches. A critical step in HIV infection is the interaction between the viral envelope protein gp120 and CD4+ receptors on host cells, making gp120 an attractive therapeutic target. This study aimed to identify potential inhibitors that disrupt the gp120-CD4 interaction through computational methods. Using an integrated approach combining multiple sequence alignment, phylogenetic analysis, structure prediction, ADME analysis, Molecular docking studies and toxicity profiling identified Epigallocatechin gallate (EGCG) as a promising lead inhibitor of the gp120-CD4 interaction, with a binding affinity of - 6.378 kcal/mol. The stability of the gp120-EGCG complex was validated through 100 ns molecular dynamics simulations and free binding energy calculations, where ΔGBind was calculated to be - 69.7 04 ± 37.940 kJ/mol. EGCG demonstrated favourable drug-like properties with no significant toxicity concerns in our computational analysis. These findings provide a foundation for future in vitro and in vivo studies to develop EGCG-based HIV entry inhibitors.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"38"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588987","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":"Structure based multi-targeted screening, docking, DFT and simulation of anticancer natural compounds against gallbladder cancer.","authors":"Suchitra Singh, Janhavi Yadav, Surbhi Singh, Sumanta Kumar Sahu, Puneet Puneet, Royana Singh","doi":"10.1007/s40203-025-00326-4","DOIUrl":"10.1007/s40203-025-00326-4","url":null,"abstract":"<p><p>Gallbladder cancer is among the sixth most common gastrointestinal malignancies, with a meager prognosis. The progression of the disease is influenced by factors like chronic inflammation and geographical locations. Current treatment options are limited and often ineffective, emphasizing the need for novel therapeutic approaches. This paper explores potential multi-targeted natural compounds by targeting key signaling proteins associated with various hallmarks of Gallbladder cancer. In silico methods, including virtual screening, molecular docking, and molecular dynamics simulations, were utilized to assess the interactions of natural compounds with five critical targets: PD-L1, VEGFR, EGFR, HER2, and c-MET. To identify potential inhibitors, a library of anticancer natural compounds was screened against each target protein. The top ten compounds for each target were then selected for precise molecular docking. A common, promising compound was identified based on the lowest binding energy. Furthermore, DFT, bioavailability, and toxicity profiles of the selected compound were analyzed, and it was subsequently subjected to molecular dynamics simulations. Among the compounds studied, 13-beta, 21-Dihydroxyeurycomanol was a common and promising compound for each protein target, exhibiting strong binding affinities and favorable interactions. DFT analysis predicted high reactivity and strong binding interactions. Furthermore, ADMET analysis showed that it was non-toxic and safe. Molecular dynamics simulation analysis revealed that 13-beta, 21-Dihydroxyeurycomanol maintains stable complexes with all the protein targets. These findings indicate that it has the potential to be an effective multi-targeted therapeutic agent for gallbladder cancer and may aid in the development of conventional medicine-based treatments for this disease.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"39"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589004","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":"In-silico repurposing of antiviral compounds against Marburg virus: a computational drug discovery approach.","authors":"Rahul Kumar Singh, Kaushik Sarkar, Rajesh Kumar Das","doi":"10.1007/s40203-025-00323-7","DOIUrl":"10.1007/s40203-025-00323-7","url":null,"abstract":"<p><p>The Marburg virus (MARV), a member of the family Filoviridae, is a highly pathogenic virus causing severe hemorrhagic fever with extremely high mortality in humans and non-human primates. The MARV exhibits clinical and epidemiological features almost identical to those of the Ebola virus, no licensed vaccines or antiviral treatments have been developed yet for MARV. However, only a few treatments that remain uncertain of the disease are available to help bring a case for a new therapeutic approach. Considering the non-availability of any standard drug we have planned to identify potential inhibitors of VP24 (PDB ID: 4OR8) through a computational drug repurposing process. The workflow includes: identifying a druggable pocket on VP24, screening of FDA-approved antivirals via molecular docking, assessing the stability using molecular dynamics simulations, and estimating binding affinity through MM-PBSA calculations. After going through the analysis, the compound Bictegravir manifests as a hit compound which will undergo in vitro and in vivo validation to confirm its efficacy against MARV.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00323-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"41"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588994","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}