Carbohydrate-Based Derivatives Act as Potential Antimicrobial and Influenza Virus Inhibitors: In vitro and In silico Approaches

A wide range of carbohydrate-derived drugs are currently utilised worldwide as antifungal, antibacterial and anticancer drugs. In this context, our research group focused on designing and synthesising new derivatives of methyl α-D-mannopyranoside (1, MDM) and exploring its antiviral and antibacterial properties through both experimental and computational approaches. Seven MDM derivatives (2–7) were synthesised via selective acylation and fully characterised using spectroscopic techniques. In vitro antibacterial activity was evaluated by MIC and MBC assays, while in silico analyses included PASS prediction, density functional theory calculations, molecular docking, and molecular dynamics simulations against influenza A neuraminidase (H1N1, PDB ID: 7XGC). Compounds 3 and 5 exhibited the most significant antibacterial activity against both Gram-positive and Gram-negative strains, with compound 5 showing superior MIC and MBC values. Computational studies revealed favourable electronic properties for the active compounds. Docking and molecular dynamics analyses identified compounds 6 and 7 as the most potent neuraminidase binders, forming stable interactions with key catalytic residues commonly involved in known neuraminidase inhibitors. The combined in vitro and in silico findings highlight acylated MDM derivatives as promising dual-action antibacterial and antiviral scaffolds, with compound 5 emerging as a potential antibacterial lead and compounds 6 and 7 as promising candidates for anti-influenza drug development.