Molecular Docking, DFT, ADMET, and PASS-based Evaluations of Methyl β-DGalactopyranoside Derivatives as Yellow Fever Virus Inhibitors

Carbohydrate-based scaffolds represent an attractive framework for the design of novel therapeutic agents because of their structural diversity, biocompatibility, and potential for selective biological interactions. Among them, galactopyranoside derivatives have drawn increasing attention owing to their pharmacological applications, particularly as antimicrobial and anticancer agents. In this study, an assortment of novel methyl β-D-galactopyranoside (1, MGalP) derivatives was evaluated for their thermodynamic stability, electronic properties, pharmacokinetics, and biological potential via in silico approaches. Density functional theory (DFT) calculations revealed that structural modifications enhanced molecular stability, polarizability, and reactivity. Molecular docking studies against yellow fever virus (YFV) (PDB ID: 6IW5) demonstrated favorable binding affinities (−5.5 to) compared with those of the parent compound. Compound 5 exhibited the greatest binding affinity of −7.0 kcal/mol. Strong interactions occurred with the amino acid residues TYR225 and TYR354, alongside PHE240, PHE339, LEU394, HIS227, ASP189, and GLY409. These findings suggest that aromatic and long-chain acyl modifications significantly improve binding properties. Pharmacokinetic profiling through ADMET prediction confirmed high intestinal absorption, good blood–brain barrier permeability, and acceptable solubility for most derivatives. PASS prediction further revealed promising antifungal and antiviral activities, suggesting the potential of these compounds as multifunctional drug candidates.