Lignin-based Mucin-mimicking Antiviral Hydrogels with Enzyme Stability and Tunable Porosity

20 March 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Mucus is a complex hydrogel acting as a defensive and protective barrier in various parts of the human body. The structure and composition of mucus play an important role in maintaining barrier properties by acting as a filter for the diffusion of biomolecules and pathogens. The rise in viral infections has underscored the importance of advancing research into mucus-mimicking hydrogels for the efficient design of antiviral agents. However, the performance of an antiviral strategy should not only be assessed based on its efficacy in inhibiting infections but also based on its sustainability. 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 were equipped with sulfate moieties, which are known binding partners for many viruses including SARS-CoV-2 and herpes viruses. In addition, crosslinking the synthesized inhibitors yielded hydrogels that mimicked native mucus with respect to surface functionality and rheology. It is found that the degree of sulfation has a very strong impact on the mesh size distribution of the hydrogels, which provides a new means to fine-tune 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 Escherichia coli (E. coli). For HSV-1 and E. coli, these measurements showed a reduction in plaque (HSV-1) and colony-forming units (E. coli) by more than 4 orders of magnitude, indicating potent inhibition by the lignin-based hydrogels. Taken together, the sulfated lignin hydrogel is an excellent scaffold for large-scale synthesis of sustainable, biocompatible, and highly efficient pathogen-binding inhibitors.


Antiviral hydrogels
Tunable porosity
Enzyme stability and rheology

Supplementary materials

Lignin Functionalization for Development of Mucin-mimicking Antiviral Hydrogels with Enzyme Stability and Tunable Porosity
31P NMR Analysis, Size Exclusion Chromatography (SEC) and Elemental Analysis, Calculations of the maximum weight % of sulfur in each subunit of lignin, Particle Size distribution analysis, UV-visible Spectrophotometric Analysis, FTIR analysis, Rheology of hydrogels, Scanning Electron Microscopy Analysis, Swelling capacity: evaluation of rheological properties after reswelling of hydrogels, Microscopy Analysis images of HSV-1 inhibition, Influenza A inhibition


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