Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors

Divalent inhibitors
of the neuraminidase enzyme (NA) of the Influenza
A virus were synthesized with vastly different spacers. The spacers
varied from 14 to 56 atoms and were relatively rigid by way of the
building blocks and their connection by CuAAC. As the ligand for these
constructs, a Δ4-β-d-glucoronide was
used, which can be prepared form N-acetyl glucosamine.
This ligand showed good NA inhibitory potency but with room for improvement
by multivalency enhancement. The synthesized compounds showed modest
potency enhancement in NA activity assays but a sizeable potency increase
in a 4-day cytopathic effect assay. The demonstration that the compounds
can also inhibit hemagglutinin in addition to NA may be the cause
of the enhancement.