%0 Journal Article
%T Chemoenzymatic synthesis of sialyl-α2,3-lactoside-functionalized BSA conjugate inhibits influenza infection.
%A Xue M
%A Tan L
%A Zhang S
%A Wang JN
%A Mi X
%A Si W
%A Qiao Y
%A Lao Z
%A Meng X
%A Yang Y
%J Eur J Med Chem
%V 276
%N 0
%D 2024 Oct 5
%M 38968785
%F 7.088
%R 10.1016/j.ejmech.2024.116633
%X 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.