{Reference Type}: Journal Article
{Title}: Chemoenzymatic synthesis of sialyl-α2,3-lactoside-functionalized BSA conjugate inhibits influenza infection.
{Author}: Xue M;Tan L;Zhang S;Wang JN;Mi X;Si W;Qiao Y;Lao Z;Meng X;Yang Y;
{Journal}: Eur J Med Chem
{Volume}: 276
{Issue}: 0
{Year}: 2024 Oct 5
{Factor}: 7.088
{DOI}: 10.1016/j.ejmech.2024.116633
{Abstract}: Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)-bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains.