Local and Noninvasive\nGlyco-Virus Checkpoint Nanoblockades Restrict Sialylation for Prolonged\nBroad-Spectrum Epidemic Virus Therapy

The\ncoronavirus disease 2019 (COVID-19) pandemic has\ndriven major advances in virus research. The role of glycans in viral\ninfection has been revealed, with research demonstrating that terminal\nsialic acids are key receptors during viral attachment and infection\ninto host cells. However, there is an urgent demand for universal\ntools to study the mechanism of sialic acids in viral infections,\nas well as to develop therapeutic agents against epidemic viruses\nthrough the downregulation of terminal sialic acid residues on glycans\nacting as a glyco-virus checkpoint to accelerate virus clearance.\nIn this study, we developed a robust sialic acids blockade tool termed\nlocal and noninvasive glyco-virus checkpoint nanoblockades (LONG NBs),\nwhich blocked cell surface sialic acids by endogenously and continuously\ninhibiting the de novo sialic acids biosynthesis pathway. Furthermore,\nLONG NBs could accurately characterize the sialic acid-dependent profiles\nof multiple virus variants and protected the host against partial\nSARS-CoV-2, rotavirus, and influenza A virus infections after local\nand noninvasive administration. Our results suggest that LONG NBs\nrepresent a promising tool to facilitate in-depth research on the\nmechanism of viral infection, and serve as a broad-spectrum protectant\nagainst existing and emerging viral variants via glyco-virus checkpoint\nblockade.