The seasonal and pandemic outbreaks of the influenza A virus (IAV) have always challenged public health. Viruses bind to the host cell surfaces by multivalent interactions between viral glycoproteins and cellular receptors on the cell. Therefore, inhibitors that can either completely block the virus adhesion onto cells or inhibit both the binding and release of virus particles from cells can be efficient for virus infection inhibition. In this project, first, the geometrical requirements for an efficient infection inhibition of IAV were unraveled using sialylated polyglycerols (PGSAs). A comparison of binding and inhibition constants revealed that the linear PGSA sterically shielded the virus surface better and outperformed the dendritic PG analogs and the commercially available oseltamivir carboxylate for the IAV infection <i>in vivo</i>. The optimized LPGSA was transformed into a flexible 3D ~ 250 nm-sized nanogel which could deform and adapt onto the virus surface via multivalent binding with hemagglutinin glycoproteins receptors on the virus surface (Figure 1a). This caused a complete blockage of the virus-cell adhesion thus prevented infection. Similarly, the flexible 2D-sialylated thermally reduced graphene oxide sheets were optimized to bind and wrap a number of IAVs (Figure 1b). Finally, glycosylated polymer-based inhibitors with a dual-mode action by inhibiting both the virus binding and budding from the infected cells were optimized. These nano-inhibitors were broadly active against a number of different IAV strains at picomolar concentrations post-infection.

Glycosylated biomaterials for meeting the challenge of influenza A virus

ACS Fall 2021

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