Computational exploration of lichen secondary metabolite usnic acid: electronic properties, ADMET profiling, and antiviral potential against dengue virus NS5 protein
Küçük Resim Yok
Tarih
2025
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer/Plenum Publishers
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
This 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.
Açıklama
Anahtar Kelimeler
DFT, In silico, NS5 protein, Electronic structure, Usnic acid
Kaynak
Structural Chemistry
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
