In silico evaluation of imidazopyridine compounds targeting ACE2: molecular dynamics and binding energy analysis

as a lead candidate with the highest binding affinity among all tested derivatives (Glide score: -9.97 kcal/mol; MM-GBSA: -79.26 kcal/mol). This compound formed stable interactions with catalytic residues and preserved structural integrity throughout simulations. Principal component analysis revealed three conformational states, indicating that compound 28 maintains stable binding while preserving the conformational flexibility necessary for catalytic function. These results identify imidazopyridines as candidate binders for experimental validation and establish a computational framework to guide future experimental studies of host-directed ACE2 modulators.