Lignin-Based Mucus-Mimicking Antiviral Hydrogels with Enzyme Stability and Tunable Porosity

Mucus is a complex hydrogel that acts as a defensive and protective barrier in various parts of the human body. The rise in the level of viral infections has underscored the importance of advancing research into mucus-mimicking hydrogels for the efficient design of antiviral agents. Herein, we demonstrate the gram-scale synthesis of biocompatible, lignin-based virus-binding inhibitors that reduce waste and ensure long-term availability. The lignin-based inhibitors are equipped with sulfate moieties, which are known binding partners for many viruses, including SARS-CoV-2 and herpes viruses. In addition, cross-linking the synthesized inhibitors yielded hydrogels that mimicked native mucus concerning surface functionality and rheology. The degree of sulfation exhibits a very strong impact on the mesh size distribution of the hydrogels, which provides a new means to fine-tune the steric and electrostatic contributions of the virus-hydrogel interaction. This feature strongly impacts the sequestration capability of the lignin-based hydrogels, which is demonstrated by infection inhibition assays involving human herpes simplex virus 1, influenza A viruses, and the bacterium <i>Escherichia coli</i> (<i>E. coli</i>). These measurements showed a reduction in plaque-forming units (HSV-1) and colony-forming units (<i>E. coli</i>) by more than 4 orders of magnitude, indicating the potent inhibition by the lignin-based hydrogels.