Self-Assembled Glutathione-Nucleotide Supramolecular Hydrogels with Intrinsic Antiviral, Antibacterial, and Anticancer Activities

Small peptides exhibit remarkable antimicrobial and biological functions, yet their translation into biomaterials often requires chemical modifications that can compromise their native functionalities. Physically cross-linked hydrogels involving noncovalent interactions can retain pristine biomolecules, enabling their functional integration. Here, we present a facile strategy for constructing all-biomolecular hydrogels through the noncovalent integration of glutathione and guanosine monophosphate. The spontaneous formation of transparent, robust, and physically cross-linked hydrogels occurs via G-quadruplex assembly, preserving inherent biomolecular functionality. These hydrogels demonstrate good mechanical strength, broad pH stability, and self-healing behavior. Morphological analysis reveals protocell-like spherical intermediates, eventually yielding helical fibrillar networks. The supramolecular fibers exhibit dose-dependent cytocompatibility with selective bioactivities, suitable for biomedical applications. In vitro studies confirmed pronounced antiviral efficacy against Epstein-Barr virus and SARS-CoV-2, alongside broad-spectrum antibacterial efficacy. Additionally, the fibers induced apoptosis in gastric cancer cells. The viscoelastic and shape-sustaining behavior of these hydrogels holds potential scope to develop antimicrobial coating materials.