Mucus is the first defense barrier against viruses in the human immune system. Inspired by the mucus structure, we designed a highly sulfated hydrogel to bind viruses and prevent infection of the underlying cells. The hydrogel was formed by gelation of sulfated cellulose nanofiber (SCNF) with Ca2+. SCNF exhibited a mucin-like nanofiber structure with high numbers of sulfated groups. Based on the electrostatic interactions with a virus, SCNF could efficiently inhibit herpes simplex virus-1 (HSV-1) infection with a half-maximal inhibitory concentration (IC50) of 0.43 μg/mL, which is comparable to that of heparin (IC50 = 0.30 μg/mL). Benefiting from the multiporous structure and sulfate groups, the Ca2+-SCNF hydrogel could efficiently trap HSV-1 and inhibit the virus from attacking the underlying cells in a transwell model. Furthermore, SCNF also inhibited SARS-CoV-2 infection in a similar experimental setting. By integrating the advantages of high and broad-spectrum virus inhibitory activity as well as low toxicity, it is believed that the Ca2+-SCNF hydrogel can promote the development of highly biocompatible and efficient antiviral material with “binding and inhibition” capability and other diverse strategies.
