Recent Anti-Influenza Strategies in Multivalent Sialyloligosaccharides and Sialylmimetics Approaches

Sialic acid-containing oligosaccharides expressed on the respiratory tract epithelial cell surface are involved in influenza virus infection in both virus attaching and detaching processes. Therefore, inhibition of sialic acid-binding processes provides rational anti-influenza strategies. Previous exploring efforts using monosaccharide sialic acid-bearing macromolecules provided proof of concept for multivalent hemagglutinin inhibition. However, the monosaccharide sialic acid cannot account for the molecular determinant of virus receptor-binding specificity in the context of the whole sialyloligosaccharide receptor. On the other hand, neuraminidase inhibition efforts using sialylmimetics have resulted into two antiinfluenza drugs, zanamivir and oseltamivir, which have been shown to reduce both the severity and duration of influenza illness. Nevertheless, the usage of monomeric sialylmimetics requires relatively large amounts of expensive compounds, which may also induce virus resistance and side effect. Therefore, it is critical to develop new antiinfluenza drugs and improve the current antiinfluenza drugs. This review highlights recent explorations of multivalent sialyloligosaccharides-based influenza virus adhesion inhibition strategy and multivalent sialylmimetics-based influenza virus detachment inhibition strategy for these efforts.