DFT Computation, Molecular Docking, MD Simulation, and Pharmacokinetic Analyses of Potent Glucopyranoside Derivatives Targeting DENV2 RdRp and <i>Escherichia coli</i> DNA GyrB

ABSTRACT The pervasive challenge of infectious diseases caused by viral and bacterial pathogens, including the rapidly emerging dengue virus (DENV) and antibiotic‐resistant Escherichia coli , necessitates the formulation of novel therapeutic agents. This study focused on a series of previously synthesized potential methyl α‐ D ‐glucopyranoside (MGP) derivatives ( 2 – 6 ) to explore their efficacy as antiviral and antibacterial agents via a computational approach. Density functional theory (DFT) was employed to determine the structural and chemical properties of the derivatives. Atomic partial charge analysis and MEP mapping provided insight into the electronic distribution and potential interaction sites with biological targets. Molecular docking studies were conducted against two critical biological targets: the allosteric N‐pocket of DENV2 RNA‐dependent RNA polymerase (RdRp) and the ATP‐binding site of Escherichia coli DNA gyrase subunit B (GyrB). Among the ligands, compound 3 showed the highest binding affinity of −8.3 kcal/mol against RdRp and −6.6 kcal/mol against GyrB. A 100 ns MD simulation study suggested that compound 3 exhibited a stable conformation against both proteins. Additionally, PCA and MM–GBSA analyses also indicated favorable binding. The PASS prediction revealed increased biological activity of the compounds. Drug‐likeness and pharmacokinetic studies suggested that the derivatives possess drug‐like properties and exhibit minimal unwanted effects, indicating their significant medicinal potential.