Computational exploration of lichen secondary metabolite usnic acid: electronic properties, ADMET profiling, and antiviral potential against dengue virus NS5 protein

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dc.contributor.authorMusatat, Ahmad Badreddin
dc.contributor.authorSevinc, Omer Seyfettin
dc.date.accessioned2025-10-11T20:48:44Z
dc.date.available2025-10-11T20:48:44Z
dc.date.issued2025
dc.departmentDüzce Üniversitesien_US
dc.description.abstractThis study comprehensively evaluates the lichen-derived usnic acid (UA) as a potential antiviral agent targeting the dengue virus NS5 protein. Density functional theory (DFT) employs B3LYP/PBE0 methodologies alongside def2-SVP/TZVP basis sets, revealing UA's electronic profile: moderate HOMO-LUMO gaps (3.80-4.24 eV), high electrophilicity (16.25-20.47 eV), and solvation-induced polarization (dipole moments up to 5.23 Debye). Molecular electrostatic potential (MEP) and reduced density gradient (RDG) analyses identified reactive oxygen sites and intramolecular hydrogen bonding, which are critical for biological interactions. ADMET predictions highlighted favorable drug-like properties (MW = 344.09 g/mol, HIA = 99.12%) but flagged liabilities, including poor solubility (logS = - 4.34), high plasma protein binding (97.16%), hepatotoxicity (DILI probability = 0.991), and CYP-mediated metabolism (CYP2C9/2C19 inhibition > 0.89). Molecular docking demonstrated UA's superior binding affinity (- 8.03 kcal/mol) to NS5 compared to the control ligand, driven by hydrogen bonds with Asp146/Val132 and hydrophobic interactions. However, rapid clearance (t(1)/(2) = 1.45 h) and toxicity risks necessitate structural optimization. This work positions UA as a promising scaffold for antiviral development, contingent on mitigating metabolic instability and toxicity through targeted modifications. The integration of quantum chemical, pharmacokinetic, and docking analyses provides a robust framework for advancing therapeutics derived from UA.en_US
dc.identifier.doi10.1007/s11224-025-02562-y
dc.identifier.issn1040-0400
dc.identifier.issn1572-9001
dc.identifier.scopus2-s2.0-105011039192en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1007/s11224-025-02562-y
dc.identifier.urihttps://hdl.handle.net/20.500.12684/22062
dc.identifier.wosWOS:001532216000001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherSpringer/Plenum Publishersen_US
dc.relation.ispartofStructural Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmzKA_WOS_20250911
dc.subjectDFTen_US
dc.subjectIn silicoen_US
dc.subjectNS5 proteinen_US
dc.subjectElectronic structureen_US
dc.subjectUsnic aciden_US
dc.titleComputational exploration of lichen secondary metabolite usnic acid: electronic properties, ADMET profiling, and antiviral potential against dengue virus NS5 proteinen_US
dc.typeArticleen_US

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