{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:20:05Z","timestamp":1791516005239,"version":"4.3.4"},"reference-count":143,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Dengue Fever continues to pose a global threat due to the widespread distribution of its vector mosquitoes, <jats:italic>Aedes aegypti<\/jats:italic> and <jats:italic>Aedes albopictus<\/jats:italic>. While the WHO-approved vaccine, Dengvaxia, and antiviral treatments like Balapiravir and Celgosivir are available, challenges such as drug resistance, reduced efficacy, and high treatment costs persist. This study aims to identify novel potential inhibitors of the Dengue virus (DENV) using an integrative drug discovery approach encompassing machine learning and molecular docking techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Utilizing a dataset of 21,250 bioactive compounds from PubChem (AID: 651640), alongside a total of 1,444 descriptors generated using PaDEL, we trained various models such as Support Vector Machine, Random Forest, k-nearest neighbors, Logistic Regression, and Gaussian Na\u00efve Bayes. The top-performing model was used to predict active compounds, followed by molecular docking performed using AutoDock Vina. The detailed interactions, toxicity, stability, and conformational changes of selected compounds were assessed through protein-ligand interaction studies, molecular dynamics (MD) simulations, and binding free energy calculations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We implemented a robust three-dataset splitting strategy, employing the Logistic Regression algorithm, which achieved an accuracy of 94%. The model successfully predicted 18 known DENV inhibitors, with 11 identified as active, paving the way for further exploration of 2683 new compounds from the ZINC and EANPDB databases. Subsequent molecular docking studies were performed on the NS2B\/NS3 protease, an enzyme essential in viral replication. ZINC95485940, ZINC38628344, 2\u2032,4\u2032-dihydroxychalcone and ZINC14441502 demonstrated a high binding affinity of \u22128.1, \u22128.5, \u22128.6, and \u22128.0\u00a0kcal\/mol, respectively, exhibiting stable interactions with His51, Ser135, Leu128, Pro132, Ser131, Tyr161, and Asp75 within the active site, which are critical residues involved in inhibition. Molecular dynamics simulations coupled with MMPBSA further elucidated the stability, making it a promising candidate for drug development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, this integrative approach, combining machine learning, molecular docking, and dynamics simulations, highlights the strength and utility of computational tools in drug discovery. It suggests a promising pathway for the rapid identification and development of novel antiviral drugs against DENV. These <jats:italic>in silico<\/jats:italic> findings provide a strong foundation for future experimental validations and <jats:italic>in-vitro<\/jats:italic> studies aimed at fighting DENV.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fchem.2024.1510029","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T06:37:01Z","timestamp":1735022221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Machine learning and molecular docking prediction of potential inhibitors against dengue virus"],"prefix":"10.3389","volume":"12","author":[{"given":"George","family":"Hanson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daveson I. B.","family":"Kepgang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke S.","family":"Zondagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Tem Bueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Asante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soham A.","family":"Shirolkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Kisaakye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hem","family":"Bondarwad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaitan I.","family":"Awe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"32483","DOI":"10.1021\/acsomega.3c02607","article-title":"Finding lead compounds for dengue antivirals from a collection of old drugs through in silico target prediction and subsequent in vitro validation","volume":"8","author":"Abdullah","year":"2023","journal-title":"ACS Omega"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1353081","DOI":"10.3389\/fgene.2024.1353081","article-title":"Exploring the causal effect of omega-3 polyunsaturated fatty acid levels on the risk of type 1 diabetes: a Mendelian randomization study","volume":"15","author":"Abolo","year":"2024","journal-title":"Front. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"Gromacs: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B4","doi-asserted-by":"publisher","first-page":"107766","DOI":"10.1016\/j.compbiolchem.2022.107766","article-title":"EBOLApred: a machine learning-based web application for predicting cell entry inhibitors of the Ebola virus","volume":"101","author":"Adams","year":"2022","journal-title":"Comput. Biol. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"100447","DOI":"10.1016\/j.phyplu.2023.100447","article-title":"In silico screening of phytochemicals from dissotisrotundifolia against plasmodium falciparum dihydrofolate reductase","volume":"3","author":"Adams","year":"2023","journal-title":"Phytomedicine Plus"},{"key":"B6","doi-asserted-by":"publisher","first-page":"963","DOI":"10.3390\/cimb44020064","article-title":"Molecular structure-based screening of the constituents of calotropis procera identifies potential inhibitors of diabetes mellitus target alpha glucosidase","volume":"44","author":"Adinortey","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"100734","DOI":"10.1016\/j.imu.2021.100734","article-title":"Molecular modelling and de novo fragment-based design of potential inhibitors of beta-tubulin gene of Necatoramericanus from natural products","volume":"26","author":"Agyapong","year":"2021","journal-title":"Inf. Med. Unlocked"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1101\/2024.01.20.576448","article-title":"Multiple sclerosis stages and their differentially expressed genes: a bioinformatics analysis","author":"Alaya","year":"2024"},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.3390\/v12040367","volume-title":"Structure-based design of antivirals against envelope glycoprotein of dengue virus","author":"Anasir","year":"2020"},{"key":"B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1109\/IJCNN.2018.8489567","article-title":"Towards predicting dengue fever rates using convolutional neural networks and street-level images","volume-title":"2018 international joint conference on neural networks (IJCNN)","author":"Andersson","year":"2018"},{"key":"B11","doi-asserted-by":"publisher","first-page":"8180","DOI":"10.3390\/ijms24098180","article-title":"Using machine learning and molecular docking to leverage urease inhibition data for virtual screening","volume":"24","author":"Aniceto","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1351737","DOI":"10.3389\/fcimb.2024.1351737","article-title":"Identifying potential monkeypox virus inhibitors: an in silico study targeting the A42R protein","volume":"14","author":"Ashley","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"653","DOI":"10.3390\/biom11050653","article-title":"Computational identification of potential anti-inflammatory natural compounds targeting the p38 mitogen-activated protein kinase (Mapk): implications for Covid-19-induced cytokine storm","volume":"11","author":"Asiedu","year":"2021","journal-title":"Biomolecules"},{"key":"B14","doi-asserted-by":"publisher","first-page":"628","DOI":"10.12688\/f1000research.14880.4","article-title":"SeqAcademy: an educational pipeline for RNA-Seq and ChIP-Seq analysis","volume":"7","author":"Ather","year":"2018","journal-title":"F1000Research"},{"key":"B15","doi-asserted-by":"publisher","first-page":"101143","DOI":"10.1016\/j.imu.2022.101143","article-title":"Comparative study between molecular and genetic evolutionary analysis tools using African SARS-CoV2 variants","volume":"36","author":"Awe","year":"2023","journal-title":"Inf. Med. Unlocked"},{"key":"B16","doi-asserted-by":"publisher","first-page":"gigabyte143","DOI":"10.46471\/gigabyte.143","article-title":"NeuroVar: an open-source tool for the visualization of gene expression and variation data for biomarkers of neurological diseases","volume":"2024","author":"Ben","year":"2024","journal-title":"Gigabyte"},{"key":"B17","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/S0140-6736(20)30414-1","article-title":"Efficacy of a tetravalent dengue vaccine in healthy children aged 4\u201316 years: a randomised, placebo-controlled, phase 3 trial","volume":"395","author":"Biswal","year":"2020","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1186\/s12936-020-03512-1","article-title":"Characterisation of plasmodial transketolases and identification of potential inhibitors: an in silico study","volume":"19","author":"Boateng","year":"2020","journal-title":"Malar. J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1128\/AAC.01429-12","article-title":"A novel inhibitor of dengue virus replication that targets the capsid protein","volume":"57","author":"Byrd","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"B21","first-page":"2708","volume-title":"Suitability of European climate for the Asian tiger mosquito","author":"Caminade","year":"2012"},{"key":"B22","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1128\/AAC.04177-14","article-title":"The bioactive lipid 4-hydroxyphenyl retinamide inhibits Flavivirus replication","volume":"59","author":"Carocci","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B23","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.36461.014","volume-title":"How small-molecule inhibitors of dengue-virus infection interfere with viral membrane fusion","author":"Chao","year":"2018"},{"key":"B24","first-page":"363","article-title":"The development, optimization and validation of an assay for high throughput antiviral drug screening against dengue virus","volume":"2","author":"Che","year":"2009","journal-title":"Int. J. Clin. Exp. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/S12929-018-0462-0","article-title":"Dengue virus non-structural protein 1: a pathogenic factor, therapeutic target, and vaccine candidate","volume":"25","author":"Chen","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"B144","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/978-1-62703-050-2_11","article-title":"Molecular dynamics","volume":"929","author":"Cheng","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"205","DOI":"10.4103\/ajim.ajim_45_23","article-title":"Study of dengue fever in an epidemic - a single centre observational study at tertiary care hospital","volume":"12","author":"Chikkaveeraiah","year":"2024","journal-title":"APIK J. Intern. Med."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1101\/2023.01.26.522643","article-title":"Multi-omics data integration approach identifies potential biomarkers for Prostate cancer","author":"Chikwambi","year":"2023","journal-title":"bioRxiv"},{"key":"B28","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.chembiol.2022.10.003","article-title":"Bortezomib inhibits ZIKV\/DENV by interfering with viral polyprotein cleavage via the ERAD pathway","volume":"30","author":"Ci","year":"2023","journal-title":"Cell. Chem. Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"123836","DOI":"10.1016\/j.fuel.2022.123836","article-title":"A systematic method for selecting molecular descriptors as features when training models for predicting physiochemical properties","volume":"321","author":"Comesana","year":"2022","journal-title":"Fuel"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1177\/1178122X17695836","article-title":"Trends of dengue disease epidemiology","volume":"8","author":"Cucunawangsih","year":"2017","journal-title":"Virology Res. Treat."},{"key":"B31","doi-asserted-by":"publisher","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4528","DOI":"10.1021\/acsomega.3c07338","article-title":"Machine learning, molecular docking, and dynamics-based computational identification of potential inhibitors against lung cancer","volume":"9","author":"Das","year":"2024","journal-title":"Mach. Learn. Mol. Docking, Dynamics-Based Comput. Identif. Potential Inhibitors against Lung Cancer"},{"key":"B33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1145\/1143844.1143874","article-title":"The relationship between Precision-Recall and ROC curves","volume-title":"Proceedings of the 23rd international conference on machine learning","author":"Davis","year":"2006"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1161\/CIRCULATIONAHA.115.001593","article-title":"Machine learning in medicine","volume":"132","author":"Deo","year":"2015","journal-title":"Circulation"},{"key":"B35","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/B978-0-12-814423-7.00005-8","article-title":"Physicochemical, pharmaceutical, and biological considerations in GIT absorption of drugs","volume-title":"Dosage form design considerations","author":"Devadasu","year":"2018"},{"key":"B36","doi-asserted-by":"publisher","first-page":"7367","DOI":"10.1128\/JVI.00632-13","article-title":"The small molecules AZD0530 and dasatinib inhibit dengue virus RNA replication via Fyn kinase","volume":"87","author":"de Wispelaere","year":"2013","journal-title":"J. Virology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1186\/s12864-019-5952-2","article-title":"geneHummus: an R package to define gene families and their expression in legumes and beyond","volume":"20","author":"Die","year":"2019","journal-title":"BMC Genomics"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1073\/pnas.1718910115","article-title":"Structural flexibility and protein adaptation to temperature: molecular dynamics analysis of malate dehydrogenases of marine molluscs","volume":"115","author":"Dong","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B39","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.clindermatol.2021.01.021","article-title":"Oral and cutaneous manifestations of viral and bacterial infections: not only COVID-19 disease","volume":"39","author":"Drago","year":"2021","journal-title":"Clin. Dermatology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.coviro.2020.09.005","article-title":"Historical discourse on the development of the live attenuated tetravalent dengue vaccine candidate TV003\/TV005","volume":"43","author":"Durbin","year":"2020","journal-title":"Curr. Opin. Virology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1093\/bfgp\/elw040","article-title":"Genomics, proteomics and evolution of dengue virus","volume":"16","author":"Dwivedi","year":"2017","journal-title":"Briefings Funct. Genomics"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.11.557132","article-title":"Differential expression analysis of miRNAs and mRNAs in epilepsy uncovers potential biomarkers","author":"El Abed","year":"2023","journal-title":"bioRxiv"},{"key":"B43","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/nsmb1073","article-title":"Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus","volume":"13","author":"Erbel","year":"2006","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"771","DOI":"10.3390\/v13050771","article-title":"Antiviral evaluation of uv-4b and interferon-alpha combination regimens against dengue virus","volume":"13","author":"Franco","year":"2021","journal-title":"Viruses"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1093\/infdis\/jiu319","article-title":"A nuclear transport inhibitor that modulates the unfolded protein response and provides in vivo protection against lethal dengue virus infection","volume":"210","author":"Fraser","year":"2014","journal-title":"J. Infect. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3390\/v16010045","article-title":"Anti-dengue: a machine learning-assisted prediction of small molecule antivirals against dengue virus and implications in drug repurposing","volume":"16","author":"Gautam","year":"2024","journal-title":"Viruses"},{"key":"B47","doi-asserted-by":"publisher","first-page":"4224","DOI":"10.1021\/acs.jcim.1c00683","article-title":"Machine learning models identify inhibitors of SARS-CoV-2","volume":"61","author":"Gawriljuk","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"B48","volume-title":"European Journal of Medicinal Chemistry De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus","author":"Gebhard","year":"2019"},{"key":"B49","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"B50","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.ijbiomac.2018.07.050","article-title":"MM-PBSA and per-residue decomposition energy studies on 7-Phenyl-imidazoquinolin-4(5H)-one derivatives: identification of crucial site points at microsomal prostaglandin E synthase-1 (mPGES-1) active site","volume":"119","author":"Gupta","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"bbab111","DOI":"10.1093\/bib\/bbab111","article-title":"SMMPPI: a machine learning-based approach for prediction of modulators of protein-protein interactions and its application for identification of novel inhibitors for RBD:hACE2 interactions in SARS-CoV-2","volume":"22","author":"Gupta","year":"2021","journal-title":"Briefings Bioinforma."},{"key":"B52","doi-asserted-by":"publisher","first-page":"02108699","DOI":"10.1371\/journal.pone.0210869","article-title":"Thioguanine-based DENV-2 NS2B\/NS3 protease inhibitors: virtual screening, synthesis, biological evaluation and molecular modelling","volume":"14","author":"Hariono","year":"2019","journal-title":"PLoS ONE"},{"key":"B53","doi-asserted-by":"publisher","first-page":"297277","DOI":"10.1002\/jmv.29727","article-title":"Serotype and genomic diversity of dengue virus during the 2023 outbreak in Pakistan reveals the circulation of genotype III of DENV\u20101 and cosmopolitan genotype of DENV\u20102","volume":"96","author":"Jamal","year":"2024","journal-title":"J. Med. Virol."},{"key":"B54","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511921803","volume-title":"Evaluating learning algorithms: a classification perspective","author":"Japkowicz","year":"2011"},{"key":"B55","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.drudis.2019.10.014","article-title":"A drug-likeness toolbox facilitates ADMET study in drug discovery","volume":"25","author":"Jia","year":"2020","journal-title":"Drug Discov. Today"},{"key":"B57","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1080\/10485252.2015.1010532","article-title":"A K-fold averaging cross-validation procedure","volume":"27","author":"Jung","year":"2015","journal-title":"J. Nonparametric Statistics"},{"key":"B58","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S1473-3099(20)30023-2","article-title":"Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial","volume":"20","author":"Kallas","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.3390\/electronics12112371","article-title":"A comparative analysis of cross-validation techniques for a smart and lean pick-and-place solution with deep learning","volume":"12","author":"Kee","year":"2023","journal-title":"Electron. Switz."},{"key":"B60","doi-asserted-by":"publisher","first-page":"45","DOI":"10.9734\/ajrcos\/2021\/v8i430209","article-title":"A comparative analysis and predicting for breast cancer detection based on data mining models","author":"Khorshid","year":"2021","journal-title":"Asian J. Res. Comput. Sci. May"},{"key":"B61","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1136\/pgmj.2008.078444","article-title":"Efficacy of low dose dexamethasone in severe thrombocytopenia caused by dengue fever: a placebo controlled study","volume":"85","author":"Kularatne","year":"2009","journal-title":"Postgrad. Med. J."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"g_mmpbsa\u2014a Gromacs Tool for High-Throughput MM-PBSA Calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"B63","doi-asserted-by":"publisher","first-page":"103414","DOI":"10.1016\/j.compbiomed.2019.103414","article-title":"Pharmacoinformatics-based identification of potential bioactive compounds against Ebola virus protein VP24","volume":"113","author":"Kwofie","year":"","journal-title":"Comput. Biol. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3390\/toxins11030181","article-title":"Molecular docking and dynamics simulation studies predict munc18b as a target of mycolactone: a plausible mechanism for granule exocytosis impairment in Buruli Ulcer Pathogenesis","volume":"11","author":"Kwofie","year":"","journal-title":"Toxins"},{"key":"B65","doi-asserted-by":"publisher","first-page":"e202200160","DOI":"10.1002\/cbdv.202200160","article-title":"Molecular modelling and atomistic insights into the binding mechanism of MmpL3 mtb","volume":"19","author":"Kwofie","year":"2022","journal-title":"Chem. Biodivers."},{"key":"B66","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.bcp.2017.01.005","article-title":"Pharmacological intervention for dengue virus infection","volume":"129","author":"Lai","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: multiple ligand\u2013protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"B68","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1002\/cem.651","article-title":"Genetic algorithms in chemometrics and chemistry: a review","volume":"15","author":"Leardi","year":"2001","journal-title":"J. Chemom."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.antiviral.2015.01.002","article-title":"Characterization of the activity of 2\u2019-C-methylcytidine against dengue virus replication","volume":"116","author":"Lee","year":"2015","journal-title":"Antivir. Res."},{"key":"B70","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.sajb.2024.04.045","article-title":"Molecular docking and dynamics simulation reveal withanolides as potent antivirals against dengue virus","volume":"169","author":"Lee","year":"2024","journal-title":"South Afr. J. Bot."},{"key":"B71","doi-asserted-by":"publisher","first-page":"364819","DOI":"10.1155\/2014\/364819","article-title":"Ligand-based and structure-based investigation for Alzheimer\u2019s disease from traditional Chinese medicine","volume":"2014","author":"Liao","year":"2014","journal-title":"Evidence-Based Complementary Altern. Med."},{"key":"B72","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/J.ANTIVIRAL.2018.12.016","article-title":"Dengue drug discovery: progress, challenges and outlook","volume":"163","author":"Lim","year":"2019","journal-title":"Antivir. Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"e1007996","DOI":"10.1371\/journal.ppat.1007996","article-title":"Molecular basis of dengue virus serotype 2 morphological switch from 29\u00b0C to 37\u00b0C","volume":"15","author":"Lim","year":"2019","journal-title":"PLoS Pathog."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2754","DOI":"10.3390\/biomedicines11102754","article-title":"The antiviral activity of varenicline against dengue virus replication during the post-entry stage","volume":"11","author":"Lin","year":"2023","journal-title":"Biomedicines"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.3851\/IMP1884","article-title":"Narasin, a novel antiviral compound that blocks dengue virus protein expression","volume":"16","author":"Low","year":"2011","journal-title":"Antivir. Ther."},{"key":"B76","unstructured":"Role of botanical drugs in controlling dengue virus disease\n          \n          \n            \n              Malabadi\n              R. B.\n            \n            \n              Chalannavar\n              R. K.\n            \n            \n              Supriya\n              S.\n            \n            \n              Nityasree\n              B. R.\n            \n            \n              Sowmyashree\n              K.\n            \n            \n              &Meti\n              N. T.\n            \n          \n          \n          2018"},{"key":"B77","doi-asserted-by":"publisher","first-page":"3909","DOI":"10.2174\/0929867323666160530144742","article-title":"Current tools and methods in molecular dynamics (MD) simulations for drug design","volume":"23","author":"Maricarmen","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"B78","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1128\/CMR.00035-09","article-title":"Dengue virus pathogenesis: an integrated view","volume":"22","author":"Martina","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/6397836","article-title":"Investigations on binding pattern of kinase inhibitors with PPAR \u03b3: molecular docking, molecular dynamic simulations, and free energy calculation studies","volume":"2017","author":"Mazumder","year":"2017","journal-title":"PPAR Res."},{"key":"B80","doi-asserted-by":"publisher","first-page":"3399","DOI":"10.1128\/AAC.06425-11","article-title":"Development of a robust cytopathic effect-based high-throughput screening assay to identify novel inhibitors of dengue virus","volume":"56","author":"McCormick","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B81","doi-asserted-by":"publisher","first-page":"299","DOI":"10.2147\/CLEP.S34440","article-title":"Epidemiology of dengue: past, present and future prospects","volume":"5","author":"Murray","year":"2013","journal-title":"Clin. Epidemiol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"23690","DOI":"10.1038\/srep23690","article-title":"Structure based docking and molecular dynamic studies of plasmodial cysteine proteases against a South African natural compound and its analogs","volume":"6","author":"Musyoka","year":"2016","journal-title":"Sci. Rep."},{"key":"B83","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1101\/2023.08.09.552643","article-title":"Enhanced deep convolutional neural Network for SARS-CoV-2 variants classification","author":"Mwanga","year":"2023","journal-title":"BioRxiv"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1093\/infdis\/jis470","article-title":"A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients","volume":"207","author":"Nguyen","year":"2013","journal-title":"J. Infect. Dis."},{"key":"B85","doi-asserted-by":"publisher","first-page":"11488","DOI":"10.3390\/ijms241411488","article-title":"Recent advances in machine-learning-based chemoinformatics: a comprehensive review","volume":"24","author":"Niazi","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B86","volume-title":"Computer-aided drug design and drug discovery: a prospective analysis","author":"Niazi","year":"2024"},{"key":"B87","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1128\/JVI.06225-11","article-title":"Ligand-bound structures of the dengue virus protease reveal the active conformation","volume":"86","author":"Noble","year":"2012","journal-title":"J. Virology"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1061937","DOI":"10.3389\/fcimb.2023.1061937","article-title":"Assessing the potential of NS2B\/NS3 protease inhibitors biomarker in curbing dengue virus infections: in silico vs. in vitro approach","volume":"13","author":"Norshidah","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"780855","DOI":"10.1371\/journal.pone.0078085","article-title":"AfroDb: a select highly potent and diverse natural product library from african medicinal plants","volume":"8","author":"Ntie-kang","year":"2013","journal-title":"PLoS One"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.11.557129","article-title":"Expression level analysis of ACE2 receptor gene in african-American and non-african-American COVID-19 patients","author":"Nyamari","year":"2023","journal-title":"bioRxiv"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1101\/2022.06.30.498338","article-title":"Transcriptional profiles analysis of COVID-19 and malaria patients reveals potential biomarkers in children","author":"Nzungize","year":"2022","journal-title":"bioRxiv"},{"key":"B92","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open Babel: an open chemical toolbox","volume":"3","author":"O\u2019Boyle","year":"2011","journal-title":"J. Cheminformatics"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1101\/2022.05.18.492401","article-title":"Molecular phylogenetics of HIV-1 subtypes in african populations: a case study of sub-saharan african countries","author":"Obura","year":"2022","journal-title":"bioRxiv"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1264808","DOI":"10.3389\/fchem.2023.1264808","article-title":"Computational identification of potential inhibitors targeting cdk1 in colorectal cancer","volume":"11","author":"Ogbodo","year":"2023","journal-title":"Front. Chem."},{"key":"B95","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.imu.2018.07.004","article-title":"A comparative computational genomics of Ebola Virus Disease strains: in-silico Insight for Ebola control","volume":"12","author":"Oluwagbemi","year":"2018","journal-title":"Inf. Med. Unlocked"},{"key":"B96","doi-asserted-by":"publisher","first-page":"e17181","DOI":"10.7717\/peerj.17181","article-title":"Investigating antimicrobial resistance genes in Kenya, Uganda and Tanzania cattle using metagenomics","volume":"12","author":"Omar","year":"2024","journal-title":"PeerJ"},{"key":"B97","doi-asserted-by":"publisher","first-page":"638","DOI":"10.3390\/pr8060638","article-title":"Measuring performance metrics of machine learning algorithms for detecting and classifying transposable elements","volume":"8","author":"Orozco-arias","year":"2020","journal-title":"May"},{"key":"B98","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s40506-023-00263-w","article-title":"Dengue: update on clinically relevant therapeutic strategies and vaccines","volume":"15","author":"Palanichamy Kala","year":"2023","journal-title":"Curr. Treat. Options Infect. Dis."},{"key":"B99","doi-asserted-by":"publisher","first-page":"1509407","DOI":"10.3389\/fchem.2024.1509407","article-title":"Proestrus: an open-source tool for 3D structure prediction using homology modeling","volume":"12","author":"Pawar","year":"2024","journal-title":"Front. Chem."},{"key":"B100","first-page":"2825","article-title":"Scikit-learn: machine learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res."},{"key":"B101","doi-asserted-by":"publisher","first-page":"001831","DOI":"10.1099\/jgv.0.001831","article-title":"Challenges on the development of a dengue vaccine: a comprehensive review of the state of the art","volume":"104","author":"Pintado Silva","year":"2023","journal-title":"J. General Virology"},{"key":"B102","doi-asserted-by":"publisher","first-page":"516","DOI":"10.2174\/1386207319666160506123715","article-title":"An in-silico investigation of phytochemicals as antiviral agents against dengue fever","volume":"19","author":"Powers","year":"2016","journal-title":"Comb. Chem. and High Throughput Screen."},{"key":"B103","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.3390\/v14102150","article-title":"A transcriptomics-based bioinformatics approach for identification and in vitro screening of FDA-approved drugs for repurposing against dengue virus-2","volume":"14","author":"Punekar","year":"2022","journal-title":"Viruses"},{"key":"B104","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s00894-022-05355-w","article-title":"Targeting the DENV NS2B-NS3 protease with active antiviral phytocompounds: structure-based virtual screening, molecular docking and molecular dynamics simulation studies","volume":"28","author":"Purohit","year":"2022","journal-title":"J. Mol. Model."},{"key":"B105","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3390\/tropicalmed9030060","article-title":"Potential way to develop dengue virus detection in Aedes larvae as an alternative for dengue active surveillance: a literature review","volume":"9","author":"Rachmawati","year":"2024","journal-title":"Trop. Med. Infect. Dis."},{"key":"B106","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s41182-017-0072-7","article-title":"Identification of novel antiviral of fungus-derived brefeldin A against dengue viruses","volume":"45","author":"Raekiansyah","year":"2017","journal-title":"Trop. Med. Health"},{"key":"B107","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1515\/tjb-2018-0002","article-title":"Computational exploration of antiviral activity of phytochemicals against NS2B\/NS3 proteases from dengue virus","volume":"44","author":"Rasool","year":"2019"},{"key":"B108","doi-asserted-by":"publisher","first-page":"113527","DOI":"10.1016\/j.ejmech.2021.113527","article-title":"Dengue structural proteins as antiviral drug targets: current status in the drug discovery and development","volume":"221","author":"S","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"B109","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3390\/biom11010042","article-title":"Potential medicinal plants for the treatment of dengue fever and severe acute respiratory syndrome-coronavirus","volume":"11","author":"Saleh","year":"2021","journal-title":"Biomolecules"},{"key":"B110","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1097\/INF.0b013e3182575e6a","article-title":"Use of pentoxifylline in treatment of children with dengue hemorrhagic fever","volume":"31","author":"Salgado","year":"2012","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B111","doi-asserted-by":"publisher","first-page":"6550","DOI":"10.1038\/s41598-022-10512-5","article-title":"Data-driven computational intelligence applied to dengue outbreak forecasting: a case study at the scale of the city of Natal, RN-Brazil","volume":"12","author":"Sanchez-Gendriz","year":"2022","journal-title":"Sci. Rep."},{"key":"B112","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1021\/ci500588j","article-title":"DataWarrior: an open-source program for chemistry aware data visualization and analysis","volume":"55","author":"Sander","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"B113","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s11030-021-10223-5","article-title":"Machine learning-based modeling to predict inhibitors of acetylcholinesterase","volume":"26","author":"Sandhu","year":"2022","journal-title":"Mol. Divers."},{"key":"B114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1109\/R10-HTC49770.2020.9357035","article-title":"Dengue prediction using machine learning algorithms","volume-title":"2020 IEEE 8th R10 humanitarian technology conference (R10-HTC)","author":"Sarma","year":"2020"},{"key":"B115","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1093\/infdis\/jiu377","article-title":"Repurposing of prochlorperazine for use against dengue virus infection","volume":"211","author":"Simanjuntak","year":"2015","journal-title":"J. Infect. Dis."},{"key":"B116","doi-asserted-by":"publisher","first-page":"20001633","DOI":"10.1002\/minf.202000163","article-title":"Pharmacoinformatic investigation of medicinal plants from East Africa","volume":"39","author":"Simoben","year":"2020","journal-title":"Mol. Inf."},{"key":"B117","doi-asserted-by":"publisher","first-page":"5533","DOI":"10.1128\/JVI.00365-14","article-title":"Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream mitogen-activated protein kinase signaling","volume":"88","author":"Smith","year":"2014","journal-title":"J. Virology"},{"key":"B118","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1021\/acs.jcim.5b00559","article-title":"ZINC 15 - ligand discovery for everyone","volume":"55","author":"Sterling","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"B119","doi-asserted-by":"publisher","first-page":"10429","DOI":"10.3390\/molecules170910429","article-title":"Computational prediction of blood-brain barrier permeability using decision tree induction","volume":"17","author":"Suenderhauf","year":"2012","journal-title":"Molecules"},{"key":"B120","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.aci.2018.08.003","article-title":"Classification assessment methods","volume":"17","author":"Tharwat","year":"2021","journal-title":"Appl. Comput. Inf."},{"key":"B121","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41541-023-00658-2","article-title":"Is new dengue vaccine efficacy data a relief or cause for concern?","volume":"8","author":"Thomas","year":"2023","journal-title":"Npj Vaccines"},{"key":"B122","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1248\/cpb.c17-00794","article-title":"Dengue virus and its inhibitors: a brief review","volume":"66","author":"Tian","year":"2018","journal-title":"Chem. Pharm. Bull."},{"key":"B123","doi-asserted-by":"publisher","first-page":"189","DOI":"10.4258\/hir.2021.27.3.189","article-title":"Impact of the choice of cross-validation techniques on the results of machine learning-based diagnostic applications","volume":"27","author":"Tougui","year":"2021","journal-title":"Healthc. Inf. Res."},{"key":"B124","doi-asserted-by":"publisher","first-page":"3325","DOI":"10.3390\/pr11123325","article-title":"On the development of descriptor-based machine learning models for thermodynamic properties: Part 1\u2014from data collection to model construction: understanding of the methods and their effects","volume":"11","author":"Trinh","year":"2023","journal-title":"Processes"},{"key":"B125","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"B126","volume-title":"XMGRACE, version 5.1. 19.","author":"Turner","year":"2005"},{"key":"B127","doi-asserted-by":"publisher","first-page":"e0224365","DOI":"10.1371\/journal.pone.0224365","article-title":"Machine learning algorithm validation with a limited sample size","volume":"14","author":"Vabalas","year":"2019","journal-title":"PLOS ONE"},{"key":"B128","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"B129","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.procs.2020.01.079","article-title":"A review of dimensionality reduction techniques for efficient computation","volume":"165","author":"Velliangiri","year":"2019","journal-title":"Procedia Comput. Sci."},{"key":"B130","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3390\/toxics12010087","article-title":"Artificial intelligence and machine learning methods to evaluate cardiotoxicity following the adverse outcome pathway frameworks","volume":"12","author":"Vigan\u00f2","year":"2024","journal-title":"Toxics"},{"key":"B131","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3390\/v14010044","article-title":"Potential role of Flavivirus ns2b-ns3 proteases in viral pathogenesis and anti-Flavivirus drug discovery employing animal cells and models: a review","volume":"14","author":"Wahaab","year":"2022","journal-title":"Viruses"},{"key":"B132","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3389\/fmolb.2017.00087","article-title":"Recent developments and applications of the MMPBSA method","volume":"4","author":"Wang","year":"","journal-title":"Front. Mol. Biosci."},{"key":"B133","doi-asserted-by":"publisher","first-page":"9","DOI":"10.22099\/ijvr.2018.4761","article-title":"The roles of cytochrome P450 and P-glycoprotein in the pharmacokinetics of florfenicol in chickens","volume":"19","author":"Wang","year":"","journal-title":"Iran. J. Veterinary Res."},{"key":"B134","doi-asserted-by":"publisher","first-page":"101050","DOI":"10.1016\/j.imu.2022.101050","article-title":"An assessment of traditional and genomic screening in newborns and their applicability for Africa","volume":"32","author":"Wesonga","year":"2022","journal-title":"Inf. Med. Unlocked"},{"key":"B135","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1093\/cid\/civ949","article-title":"Lovastatin for the treatment of adult patients with dengue: a randomized, double-blind, placebo-controlled trial","volume":"62","author":"Whitehorn","year":"2016","journal-title":"Clin. Infect. Dis. Official Publ. Infect. Dis. Soc. Am."},{"key":"B136","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1742-4658.2007.06178.x","article-title":"Protein crystallography for non-crystallographers, or how to get the best (but not more) from published macromolecular structures","volume":"275","author":"Wlodawer","year":"2008","journal-title":"FEBS J."},{"key":"B137","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/978-3-319-23558-5_25","article-title":"Chemometrics and predictive modelling","volume-title":"Nonclinical statistics for pharmaceutical and biotechnology industries","author":"Wu","year":"2016"},{"key":"B138","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1007\/s10875-011-9578-7","article-title":"Immunosuppressive effects and mechanisms of leflunomide in dengue virus infection of human dendritic cells","volume":"31","author":"Wu","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"B139","doi-asserted-by":"publisher","first-page":"e0006934","DOI":"10.1371\/journal.pntd.0006934","article-title":"Antivirus effectiveness of ivermectin on dengue virus type 2 in Aedes albopictus","volume":"12","author":"Xu","year":"2018","journal-title":"PLoS Neglected Trop. Dis."},{"key":"B140","doi-asserted-by":"publisher","first-page":"105674","DOI":"10.1016\/j.meegid.2024.105674","article-title":"Genomic surveillance of dengue virus in Benin","volume":"125","author":"Yadouleton","year":"2024","journal-title":"Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis."},{"key":"B141","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1002\/jcc.21707","article-title":"PaDEL-descriptor: an open source software to calculate molecular descriptors and fingerprints","volume":"32","author":"Yap","year":"2011","journal-title":"J. Comput. Chem."},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a platform for computational drug design","volume":"7","author":"Yuan","year":"2017","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."},{"key":"B143","doi-asserted-by":"publisher","first-page":"84","DOI":"10.14499\/indonesianjpharm30iss2pp84-90","article-title":"Synthesis and in silico studies of a benzenesulfonyl curcumin analogue as a new anti dengue virus type 2 (DEN2) NS2B\/NS3","volume":"30","author":"Zamri","year":"2019","journal-title":"Indonesian J. Pharm."}],"container-title":["Frontiers in Chemistry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2024.1510029\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T06:37:13Z","timestamp":1735022233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2024.1510029\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,24]]},"references-count":143,"alternative-id":["10.3389\/fchem.2024.1510029"],"URL":"https:\/\/doi.org\/10.3389\/fchem.2024.1510029","relation":{},"ISSN":["2296-2646"],"issn-type":[{"value":"2296-2646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,24]]},"article-number":"1510029"}}