In silico pharmacology最新文献

{"title":"Molecular docking and molecular dynamics simulation studies of thiazole-coumarin and thiazole-triazole conjugates against M^pro and ACE2 receptor for SARS COV-2.","authors":"Deepak Mishra, Ram Singh, Nupur S Munjal, Naresh Kumar, Prashant Kumar, Poonam, Sandeep Sharma","doi":"10.1007/s40203-025-00372-y","DOIUrl":"10.1007/s40203-025-00372-y","url":null,"abstract":"<p><p>The recent COVID-19 pandemic, which caused severe respiratory infections and multiple organ failure leading to death, has drawn the attention of researchers around the world. Several vaccines are available for protection against SARS-CoV-2. However, the frequent changes in its viral genome have raised concerns about the efficacy of current vaccines. Most of the research has focused on developing novel therapeutic agents, and till now no approved anti-viral drugs are available. The development of an effective and approved drug is a time-consuming process, so research is increasingly focusing on the screening of highly active molecules based on computer-aided drug designs. Heterocyclic moieties like coumarin, thiazole, and triazole exhibit diverse biological applications. To identify potent inhibitors of SARS-CoV-2 targets, we performed molecular docking and dynamics simulations on thiazole-coumarin and thiazole-triazole conjugates. These compounds effectively target the viral M^pro and ACE2 receptors. Based on the results obtained, RD9, RD12, RD17, and RD18 were found to be most active. These molecules make an excellent interaction with the active site of both enzyme M^pro and ACE2 with a free binding energy of - 8.33, - 7.89, - 8.61, - 8.02, - 9.87, - 9.75, - 9.49, - 9.61 kcal mol^-1 respectively which can potentially be used as a dual inhibitor. Molecular dynamics simulation studies further confirm the stability of these complexes. These findings suggest that thiazole-coumarin and thiazole-triazole conjugates can serve as potential candidates for dual inhibition of M^pro and ACE2 enzyme, and can be effectively used to control COVID-19 infection.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"84"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277139","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":"Epitope-driven vaccine design against <i>Listeria monocytogenes</i>: an in-silico approach.","authors":"Sachin Kumar, Shubham Moolchandani","doi":"10.1007/s40203-025-00365-x","DOIUrl":"10.1007/s40203-025-00365-x","url":null,"abstract":"<p><p>This study presents an in-silico approach to design a vaccine targeting Listeriolysin O (LLO) exotoxin in <i>Listeria monocytogenes</i>, a significant foodborne pathogen. Utilizing bioinformatics tools, we identified and prioritized B-cell and T-cell epitopes from the LLO sequence, ensuring non-toxicity, immunogenicity, non-allergenicity, and water solubility. The final vaccine construct, comprising 315 amino acids, was developed by combining selected epitopes with appropriate linkers and an adjuvant. Physicochemical characterization revealed favorable properties, including stability and solubility. Immune simulation using the C-ImmSim server predicted robust cellular and humoral responses, with significant increases in antibody levels and cytokine production within five days of administration in an in-silico study. Structural analysis of the vaccine construct yielded a refined 3D model with about 95% of residues in most favored regions of the Ramachandran plot. Protein-protein docking analysis using the ClusPro server predicted significant binding affinity between the vaccine construct and MHC-II receptors, with multiple hydrogen bonds and salt bridges contributing to stable interactions, as confirmed by PDBsum interaction analysis. Codon optimization for expression in <i>Escherichia coli</i> resulted in a high Codon Adaptation Index (0.977) and suitable GC content (53.59%). The optimized sequence was successfully integrated into a pET28a (+) vector in-silico. While these computational results are promising, experimental validation is necessary to confirm the vaccine's immunogenicity, safety, and efficacy against <i>L. monocytogenes</i> infection. This study demonstrates the potential of in-silico approaches in accelerating vaccine development against challenging pathogens and provides a foundation for further research into listeriosis prevention.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"83"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277137","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":"2D-QSAR and molecular docking based virtual screening and molecular dynamic simulation of the indole based herbal molecules for the discovery of potent molecules in the treatment of Alzheimer's disease.","authors":"Deepika Paliwal, Ritam Mondal, Aman Thakur","doi":"10.1007/s40203-025-00364-y","DOIUrl":"10.1007/s40203-025-00364-y","url":null,"abstract":"<p><p>Alzheimer's disease, a significant health challenge predominantly affecting the elderly, currently lacks curative treatments, with existing therapies offering only symptomatic relief. This study aimed to identify herbal indole-based molecules with therapeutic potential against Alzheimer's disease. A 2D QSAR model was developed for virtual screening, identifying five promising herbal molecules with predicted biological activity. Molecular docking studies further narrowed the candidates to three molecules-Evodiamine, Hyrtinadine A, and Lyaloside-which exhibited superior docking scores compared to the standard drug Donepezil against Crystal Structure of Recombinant Human Acetylcholinesterase (PDB Id-4ey7). Molecular dynamics simulations validated the stability of these molecules' interactions with the target receptor. These findings suggest that Evodiamine, Hyrtinadine A, and Lyaloside hold potential as leads for developing effective treatments for Alzheimer's disease. Despite the encouraging insights obtained from the molecular docking and 2D-QSAR techniques, the study is constrained by the absence of in vitro and in vivo confirmation, requiring additional experimental assessments. To determine their therapeutic potential against Alzheimer's disease, future studies should concentrate on the pharmacokinetic profiles and preclinical evaluations of the identified lead compounds.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00364-y.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"81"},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251577","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 modeling to design a multiepitope vaccine against emerging tick-borne Yezo virus and its validation through biophysics techniques.","authors":"Hassan Ayaz, Muhammad Suleman, Asad Ali Shah, Syed Ainul Abideen, Faisal Ahmad, Muhammad Ali, Sajjad Ahmad, Asia Nawaz, Hanbal Ahmad Khan, Inam Hussain, Muhammad Irfan, Yasir Waheed","doi":"10.1007/s40203-025-00370-0","DOIUrl":"10.1007/s40203-025-00370-0","url":null,"abstract":"<p><p>Globally, tickborne orthonairoviruses are regarded as a danger to public health. The new infectious virus known as Yezo virus, which is spread by tick bites, produces a condition marked by fever and a decrease in leucocytes and blood platelets. We suggest a multiepitope vaccination design that makes use of immunoinformatics technologies to combat this new danger. Sequences from Yezo virus proteins were gathered, and they allowed us to identify T-cell and linear B-cell epitopes. The vaccine design showed good physical and chemical characteristics as well as allergenicity and antigenicity. Simulations of molecular docking revealed robust contact with toll-like receptor 4. The HDOCK server generated the docking scores for protein interactions i.e. -295.74 kcal/mol for the epitopes in combined form: -281.98 kcal/mol by the epitopes obtained from nucleoprotein, and epitopes obtained from the glycoprotein shows - 262.67 kcal/mol in response to TLR4. The dynamic analysis of vaccine binding with these receptors was conducted with regards to interaction energetics and complex stability. Results showed that vaccine construct was stable throughout the simulation time intervals with strong hydrogen bonds interactions with TLR4 receptor residues. Lastly, we hypothesize that the vaccination sequence described here has a great chance of eliciting particular and protective immune responses, pending assessment of further experimental investigation.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"80"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251578","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 impact of <i>ZG16B</i> missense mutations: computational prediction of structural and functional consequences.","authors":"Jannatun Nayem Namme, Hasan Mahmud Reza, Asim Kumar Bepari","doi":"10.1007/s40203-025-00366-w","DOIUrl":"10.1007/s40203-025-00366-w","url":null,"abstract":"<p><p>Human Zymogen granule protein 16 homolog B (ZG16B), a secreted lectin, plays critical roles in tumor progression and metastasis through regulating autocrine and paracrine signaling. Its overexpression in multiple cancers, including pancreatic, colorectal, breast, ovarian, and prostate cancers, highlights its potential as a biomarker and therapeutic target. However, despite its elevated expression in multiple tumor types, the structural and functional consequences of genetic variants in ZG16B remain poorly understood. This study aimed to characterize deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in the <i>ZG16B</i> gene and evaluate their potential structural and functional effects using a comprehensive in-silico pipeline. Out of 28 nsSNPs, four high-confidence deleterious variants W97R, E117K, Y142N, and P186L were prioritized based on predictions from SIFT, PolyPhen-2, SNAP2, Meta-SNP, and PhD-SNP. Homology models were built using SWISS-MODEL, and structural impacts were assessed with HOPE, Missense3D, and DynaMut, which indicated disrupted hydrogen bonding, altered hydrophobic cores, and local destabilization. Results from stability prediction using DUET, iStable, and MuPro further supported the destabilizing effects. Molecular dynamics simulations (500ns) showed increased root mean square deviation (RMSD) and altered root-mean-square fluctuation (RMSF) of the variants. Additionally, protein-protein interaction analysis using STRING and molecular docking revealed reduced binding affinity between mutant ZG16B and lysozyme (LYZ), with weakened hydrogen bonding and hydrophobic interactions. These findings suggest that while ZG16B is overexpressed in tumors, deleterious mutations may impair its function, contributing to disease progression through structural destabilization and disrupted protein interactions. The present study is expected to assist future research in ZG16B mutation interpretation, variant pathogenicity, and diagnostic approaches for cancers.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00366-w.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"79"},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228065","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":"Design and in Silico evaluation of 3',4'-Dimethoxy flavonol as promising SARS-CoV-2 main protease (M^pro) inhibitor.","authors":"Neni Frimayanti, Ihsan Ikhtiarudin, Roni Ardiyansyah, Rahayu Utami, Abdi Wira Septama","doi":"10.1007/s40203-025-00368-8","DOIUrl":"10.1007/s40203-025-00368-8","url":null,"abstract":"<p><p>Flavonoids possess various biological activities, including the ability to inhibit SARS-CoV-2. This study aimed to synthesize 3',4'-dimethoxyflavonol (F34) and assess its potential as an anti-SARS-CoV-2 agent. F34 was synthesized using the Flynn-Algar-Oyamada reaction, and molecular docking studies were performed using the MOE 2022.02 software, utilizing the SARS-CoV-2 crystal structure (PDB ID: 6M2N) from the RCSB Protein Data Bank. To further investigate the binding stability of F34, pharmacophore analysis and molecular dynamics (MD) simulations were conducted. The synthesis yielded F34 at 75.23% yield, as confirmed by 1 H-NMR, FT-IR, and UV-Vis analyses. Docking results indicated that F34 interacted with key amino acid residues in the SARS-CoV-2 active site, with a binding free energy of -8.42 kcal/mol and an RMSD of 1.03. F34 forms a hydrogen bond with Gly143 and His164, and interacts with the catalytic dyad residues His41 and Cys145, which are crucial for SARS-CoV-2 inhibition. MD simulations further suggested stable hydrogen-bond interactions between F34 and Gly143/His164 at distances below 2.9 Å. These findings suggest that F34 could be a promising SARS-CoV-2 inhibitor.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00368-8.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"78"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210556","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 stigmasterol as a potential therapeutic agent for cervical cancer: insights from density functional theory (DFT) and molecular docking studies.","authors":"Udoh Ekaette Sunday, Muofunanya I Stephanie, Favour Otuonye, Dickson Oluwadamilola, Augusta A Lazarus","doi":"10.1007/s40203-025-00361-1","DOIUrl":"10.1007/s40203-025-00361-1","url":null,"abstract":"<p><p>Cervical cancer an appalling disease common amongst women worldwide, caused by human papillomavirus (HPV) with 80% increasing cases in developing countries, is reported to be persistent despite the various treatment measures. Hence, this research explores the properties of stigmasterol (SML), a biological active compound derived from <i>Costus afer</i> plant, as a drug agent for treatment of cervical cancer via density functional theory (DFT) studies and molecular docking investigation. Here, five key proteins were selected (for 4LEO, 7X8O, 5N2F, 4P7U and 2N5R) for in silico molecular docking study with SML. The DFT at ωB97XD/6-311++G (2d, 2p) level of theory was utilized and optimization of the compound was carried out in four different solvent phases, viz; acetone, ethanol, water, and gas to ascertain the level of reactivity and stability of the compound. The HOMO-LUMO energy gaps exhibited by acetone, ethanol, gas, and water were: 9.4128 eV, 9.4134 eV, 9.3140 eV, and 9.4164 eV, respectively. Interestingly, the resulting binding affinities for SML-protein interaction for 4LEO, 7X8O, 5N2F, 4P7U and 2N5R showed notable binding affinities of - 7.6 kcal/mol, - 5.2 kcal/mol, - 6.1 kcal/mol, - 5.2 kcal/mol and - 5.0 kcal/mol, respectively, as compared to the binding affinities (- 5.2 to - 7.6 kcal/mol) recorded for proteins-standard drugs interaction. The Non-covalent interactions (NCI) analysis showed predominately, van der Waals interactions in all the phases. This investigation suggest that SML can be used in the treatment and management of cervical cancer and requires further investigation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00361-1.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"77"},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153064","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":"Analysis of natural compounds identifies potential inhibitors for phosphoglucomutase of <i>Acinetobacter baumannii</i>: a computational approach.","authors":"Aishwarya Swain, Archana Pan","doi":"10.1007/s40203-025-00360-2","DOIUrl":"10.1007/s40203-025-00360-2","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> has become resistant to almost all available antibiotics in the market, emphasizing the need to develop novel antibiotics against this pathogen. The present study aims to identify potential inhibitors for phosphoglucomutase (Pgm) of <i>A. baumannii</i> by screening natural compounds. Pgm, a key enzyme involved in bacterial cell wall biosynthesis, is identified as a promising drug target. The study first employed various computational modeling tools to predict the structure of Pgm protein as its experimental structure was unavailable. After a thorough evaluation, the AlphaFold2 model (Rank 4) was chosen and energy-minimized for molecular docking study with its natural substrates, glucose-1-phosphate (G1P) and glucose-6-phosphate (G6P). Virtual screening of the natural compounds from LOTUS and CMNPD databases against Pgm identified top five compounds DMA, DPD, 2-DPD, HAP, and DTP, which exhibited better docking scores (- 8.287 kcal/mol, - 8.082 kcal/mol, - 8.082 kcal/mol, - 8.081 kcal/mol and - 7.97 kcal/mol) compared to the natural substrates G6P and G1P (- 6.225 kcal/mol, - 5.959 kcal/mol). The drug-likeness assessment of these compounds revealed that DPD had favorable pharmacokinetic profiles and was non-carcinogenic, non-irritating to the eyes, non-corrosive, and free of respiratory toxicity, representing it as a promising drug candidate. Molecular dynamics simulations and binding free energy calculations confirmed the stable interactions of DPD with Pgm, further supporting its potential as an inhibitor. Thus, the present study elucidated a natural compound as potential inhibitor against a vital protein Pgm. Further experimental studies can be carried out to understand its antibacterial properties for developing novel drugs against <i>A. baumannii</i> infections.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00360-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"76"},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082455","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":"Zebrafish and bioactive compounds: a bibliometric review.","authors":"João Paulo Lima de Oliveira, Kiara Cândido Duarte da Silva, Bianca Aparecida de Sousa, William Franco Carneiro, Moises Silvestre de Azevedo Martins, Luis David Solis Murgas, Elisângela Elena Nunes Carvalho","doi":"10.1007/s40203-025-00363-z","DOIUrl":"10.1007/s40203-025-00363-z","url":null,"abstract":"<p><p>Bibliometrics has become a crucial tool for evaluating and analyzing researchers' output. In recent decades, zebrafish has demonstrated its potential for studying oxidative stress, and the use of medicinal plants has proven essential in this context, as they are endowed with bioactive compounds that possess antioxidant properties. Thus, the aim of this study was to conduct a bibliometric review to analyze the evolution of publications concerning the concepts of \"zebrafish\" and \"bioactive compounds.\" The Web of Science (WoS) database was utilized. Data on authors, countries, most cited journals, co-authorship between countries and authors, co-occurrence of keywords, keyword co-occurrence by publication year, and co-citation of references were analyzed using VOSviewer software. A total of 170 documents were retrieved, spanning the years 2004 to 2024. Jean Luc Wolfender, the United States, and <i>PLoS One</i> were prominent among the authors, countries, and journals with the highest citations, respectively. Among the co-occurrence of keywords, the following were noteworthy: zebrafish (<i>n</i> = 60), bioactive compounds (<i>n</i> = 12), angiogenesis (<i>n</i> = 9), antioxidant (<i>n</i> = 8), oxidative stress (<i>n</i> = 8), apoptosis (<i>n</i> = 7), antioxidant activity (<i>n</i> = 7), and toxicity (<i>n</i> = 7). It was concluded that the highest number of published documents was observed in 2022. Moreover, from 2018 onward, there has been an increase in research using the zebrafish model and bioactive compounds, highlighting the field of Pharmacy/Pharmacology in the development of new drugs, with a strong emphasis on the use of medicinal plants.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"75"},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082545","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":"Chemoinformatics exploration of synthetically accessible <i>N</i>-heterocycles: uncovering new antifungal lead candidates.","authors":"Shiv Shankar Gupta, Veerbhan Kesarwani, Ravi Shankar, Upendra Sharma","doi":"10.1007/s40203-025-00359-9","DOIUrl":"10.1007/s40203-025-00359-9","url":null,"abstract":"<p><p>Fungal infections caused by <i>Candida albicans</i> pose a significant global health challenge due to their high morbidity, mortality, and the growing prevalence of drug resistance. The failure of existing antifungal agents against resistant strains underscores the urgent need for novel therapeutic alternatives. In response to this challenge, we have created an in-house library of biologically relevant nitrogenous heterocycles to screen against the resistant <i>C. albicans</i> dihydrofolate reductase (DHFR), with the aim of identifying potential antifungal leads. Using computational tools such as molecular docking and dynamics simulations, we identified two promising leads based on isoquinoline scaffold. The stability of these leads was further assessed using quantum chemical descriptor calculations. Screening results indicate that these isoquinoline-based compounds could serve as potential antifungal candidates, offering a foundation for the development of new therapies to combat resistant <i>C. albicans</i> infections. Further experimental studies, including animal model testing, are necessary to validate and confirm our findings.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00359-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"74"},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048515","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}