Chandna Sanjam, Povolotsky Tatyana L, Nie Chuanxiong, Schwartz Sophia, Wedepohl Stefanie, Quaas Elisa, Ludwig Kai, Boyakova Yulia, Bhatia Sumati, Meyer Klas, Falkenhagen Jana, Haag Rainer, Block Stephan
Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin 14195, Germany.
Faculty of Science and Engineering, Department of Chemistry, Swansea University, Singleton Campus, Swansea, Swansea SA28PP, U.K.
ACS Appl Mater Interfaces. 2025 Feb 12;17(6):8962-8975. doi: 10.1021/acsami.4c18519. Epub 2025 Jan 28.
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 (). These measurements showed a reduction in plaque-forming units (HSV-1) and colony-forming units () by more than 4 orders of magnitude, indicating the potent inhibition by the lignin-based hydrogels.
黏液是一种复杂的水凝胶，在人体各个部位起着防御和保护屏障的作用。病毒感染水平的上升凸显了推进对模拟黏液水凝胶的研究以高效设计抗病毒药物的重要性。在此，我们展示了克级规模合成的生物相容性木质素基病毒结合抑制剂，该抑制剂减少了浪费并确保了长期可用性。基于木质素的抑制剂带有硫酸根部分，硫酸根是许多病毒（包括严重急性呼吸综合征冠状病毒2和疱疹病毒）已知的结合伴侣。此外，将合成的抑制剂交联得到了在表面功能和流变学方面模拟天然黏液的水凝胶。硫酸化程度对水凝胶的网孔尺寸分布有非常强烈的影响，这为微调病毒 - 水凝胶相互作用的空间和静电作用提供了一种新方法。这一特性对基于木质素的水凝胶的螯合能力有很大影响，这在涉及人单纯疱疹病毒1、甲型流感病毒和细菌（此处原文缺失细菌名称）的感染抑制试验中得到了证明。这些测量结果显示，噬斑形成单位（单纯疱疹病毒1）和菌落形成单位（此处原文缺失具体说明）减少了超过4个数量级，表明基于木质素的水凝胶具有强大的抑制作用。
