Influenza affects about 20% of the U.S. population and better antiviral treatments for influenza are in dire need.  We report here the synthesis of multivalent inhibitors that block viral entry by competing against the binding of viral hemagglutinin (HA) for host cell-surface sialylated glycans. The inhibitors are composed of multiple copies of sialylated N-glycans on a human serum albumin (HSA) scaffold. Two methods were used to conjugate sialoglycan to the HSA scaffold. Using click chemistry, the HSA protein was modified with azide and an asparagine-linked sialoglycan was modified with an alkyne group. Then click reaction between the two provided the multivalent inhibitor. Alternatively, a direct conjugation was fulfilled using a BS(PEG)5 bi-functional linker. The density of glycans on scaffold was varied by using different ratio of sialoglycan to HSA in the conjugation.  Preliminary anti-viral assay showed that a multivalent inhibitor had higher inhibitory activity than the monomeric sialoglycan.

Strength in numbers: Multivalent inhibitors against influenza virus

244th National Meeting (2012)

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