{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:46:02Z","timestamp":1782477962800,"version":"3.54.5"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Dengue poses a persistent and widespread threat with no effective antiviral drug available till now. Several inhibitors have been developed by targeting the viral non-structural proteins including methyl transferase (NS5) of the dengue virus with possible therapeutic values. In this work, virtual screening, molecular docking, molecular dynamics simulations (200 ns), and assessments of free energy changes have been carried out to identify potential candidates from a database of flavonoids (<jats:italic>ca<\/jats:italic>. 2000) that may have good curative potential from the disease. The binding affinity of flavonoids, namely Genistein-7-glucoside (FLD1), 6\u2019\u2013O-Acetylgenistin (FLD2), 5,6-dihydroxy-2-(4-hydroxyphenyl)-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxane-2-yl]oxychromen-4-one (FLD3), Glucoliquiritigenin (FLD4), and Chrysin-7-O-glucoronide (FLD5) showed the binding affinities of \u221210.2, \u221210.2, \u221210.1, \u221210.1, \u22129.9 kcal\/mol, respectively, and possessed better values than that of the native ligand (\u22127.6 kcal\/mol) and diclofenac sodium (\u22127.3 kcal\/mol). Drug-likeness of the top five flavonoids were acceptable and no end-point toxicity was hinted by ADMET predictions. The stability of the protein-ligand complexes was accessed from 200 ns molecular dynamics simulations in terms of various geometrical parameters; RMSD, RMSF of residues, Rg, SASA, H-bond, and RPDF. The binding free energy changes of these adducts were calculated by the MM\/PBSA solvation model with negative values (from \u221238.01\u00b17.53 to \u221217.75\u00b111.03 kcal\/mol) indicating the sustained spontaneity of the forward reaction and favorability of the product formation. The geometrical and thermodynamic parameters inferred that the flavonoids could bind at the orthosteric site of the target protein of DENV-2 and could inhibit its functioning, possibly, resulting in the prevention of the disease. Overall, this study highlights the anti-DENV activity of five flavonoids, positioning them as promising candidates for further development as antiviral agents against dengue infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0301747","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T18:30:17Z","timestamp":1734028217000},"page":"e0301747","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["In silico exploration of potent flavonoids for dengue 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