In silico exploration of potent flavonoids for dengue therapeutics

PLoS ONE, Год журнала: 2024, Номер 19(12), С. e0301747 - e0301747

Опубликована: Дек. 12, 2024

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 dengue virus possible therapeutic values. In this work, virtual screening, molecular docking, dynamics simulations (200 ns), assessments free energy changes carried out to identify potential candidates from database flavonoids ( ca . 2000) that may good curative disease. The binding affinity flavonoids, namely Genistein-7-glucoside (FLD1), 6’–O-Acetylgenistin (FLD2), 5,6-dihydroxy-2-(4-hydroxyphenyl)-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxane-2-yl]oxychromen-4-one (FLD3), Glucoliquiritigenin (FLD4), Chrysin-7-O-glucoronide (FLD5) showed affinities −10.2, −10.1, −9.9 kcal/mol, respectively, possessed better values than native ligand (−7.6 kcal/mol) diclofenac sodium (−7.3 kcal/mol). Drug-likeness top five were acceptable end-point toxicity was hinted ADMET predictions. stability protein-ligand complexes accessed 200 ns in terms various geometrical parameters; RMSD, RMSF residues, Rg, SASA, H-bond, RPDF. these adducts calculated MM/PBSA solvation model negative (from −38.01±7.53 −17.75±11.03 indicating sustained spontaneity forward reaction favorability product formation. thermodynamic parameters inferred could bind at orthosteric site target protein DENV-2 inhibit its functioning, possibly, resulting prevention Overall, study highlights anti-DENV activity positioning them as promising for further development agents against infection.

Язык: Английский

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In silico exploration of potent flavonoids for dengue therapeutics

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 28, 2024

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 dengue virus possible therapeutic values. In this work, virtual screening, molecular docking, dynamics simulations (200 ns), assessments free energy changes to identify potential candidates from database flavonoids (ca. 2000) that may good curative disease. The binding affinity flavonoids, namely Genistein-7-glucoside (FLD1), 6’–O-Acetylgenistin (FLD2), 5,6-dihydroxy-2-(4-hydroxyphenyl)-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxane-2-yl]oxychromen-4-one (FLD3), Glucoliquiritigenin (FLD4), Chrysin-7-O-glucoronide (FLD5) showed affinities −10.2, −10.1, −9.9 kcal/mol, respectively, possessed better values than native ligand (−7.6 kcal/mol) diclofenac sodium (−7.3 kcal/mol). Drug-likeness these compounds was acceptable toxicity hinted ADMET predictions. stability protein-ligand complexes accessed 200 ns simulation in terms various geometrical parameters; RMSD, RMSF residues, Rg, SASA, H-bond complexes. were calculated MM-PBSA solvation model negative (less −38.01±7.53 indicating spontaneity forward reaction favorability product formation. thermodynamic parameters infer flavonoid binds at orthosteric site target protein DENV-2 could inhibit its functioning resulting prevention Overall, study highlights anti-DENV activity five positioning them as promising for further development agents against infection.

Язык: Английский

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nCoV-19 therapeutics using cucurbitacin I structural derivatives: an in silico approach

Future Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 10(1)

Опубликована: Апрель 4, 2024

Abstract Background Cucurbitacins are present in some common vegetables as secondary metabolites and used by the plants against harmful microbes. Exploration of this capability natural product based substances wide variety microbes seems relevant due to ease availability resources safety. In regard, considering current pandemic, antiviral properties these molecules with a subset Cucurbitacin I structural derivatives have been screened. The inhibition potential phytochemicals was assessed stability protein–ligand complex formed nucleocapsid protein (PDB ID: 7CDZ) SARS-CoV-2 computational methods. proposition an alternate candidate that is cost-effective efficient relative existing formulations main objective work. Results Server-based molecular docking experiments revealed CBN19 (PubChem CID: 125125068) hit among 101 test compounds, reference molecule (K31), 5 FDA-approved drugs terms binding affinities sorted out on total energies. dynamics simulations (MDS) showed moderate protein-CBN19 implied various geometrical parameters RMSD, R g , RMSF, SASA hydrogen bond count. ligand RMSD 3.0 ± 0.5 Å, RMSF C α less than smooth nature curves were calculated for adduct. free energy (− 47.19 6.24 kcal/mol) extracted from MDS trajectory using MMGBSA method indicated spontaneity reaction between protein. multiple ADMET studies predicted drug-like minimal toxicity mandate experimental verification. Conclusions Based all preliminary silico results, Cucurbitacin, could be proposed inhibitor theoretically capable curing disease. recommended further vitro vivo trials quest develop effective therapeutics plant-based COVID-19.

Язык: Английский

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Hirshfeld surface and fingerprint plot analysis of non-covalent interaction (NCI) in CuII −based catecholase models

Computational and Theoretical Chemistry, Год журнала: 2024, Номер 1238, С. 114732 - 114732

Опубликована: Июнь 25, 2024

Язык: Английский

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Cholesterol-based mesogenic Schiff’s base derivatives: Biological evaluation, photoluminescence and DFT studies

Journal of Molecular Liquids, Год журнала: 2024, Номер 410, С. 125649 - 125649

Опубликована: Июль 28, 2024

Язык: Английский

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