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

Small peptides are well known for their antimicrobial and various other biological activities. However, their practical implication requires transformation into functional materials that often involve covalent crosslinking or chemical modifications. In contrast, the pristine structure and activity of biomolecules can be preserved in physically crosslinked hydrogels enabling their functional integration. In this work, we report a facile synthetic strategy to fabricate glutathione-based hydrogels utilizing guanosine monophosphate as the gelator enabled by G-Quadruplex formation. The simple physical mixing of two components resulted in a spontaneous transparent and mechanically robust hydrogel. The hydrogels were stable in a wide pH window and showed thermo-reversibility, self-healing, thixotropic and injectable behaviour. The concentration-dependent morphological studies revealed the formation of helical fibrils takes place via protocell-like spherical intermediates. The all-biomolecule hydrogel is biocompatible, and the high water content in the matrix enables them to mimic tissue-like environment further augmenting their suitability for biological applications. In vitro cell studies revealed the potent antiviral activity of the hydrogels against EBV and SARS-CoV-2 viruses. These hydrogels also possess antibacterial activity against both gram-positive and gram-negative bacteria. qRT-PCR, cell proliferation, and EB/AO staining experiments revealed the induced cell apoptosis in gastric cancer cells upon hydrogel treatment. The multimodal bioactivities of the hydrogels can be exploited to design materials for inhibiting microbial propagation and facilitating therapeutic applications to tackle COVID-19-like outbreak situations and minimize health hazards. The viscoelastic and shape-sustaining behaviour of these hydrogels can be potentially utilized to develop antimicrobial coatings on various surfaces.