Combating DC-SIGN-mediated SARS-CoV-2 dissemination by glycan-mimicking polymers

Area of Science:

• Virology
• Carbohydrate Chemistry
• Immunology

Background:

• Many viruses utilize the dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) for cellular entry and spread.
• Inhibiting DC-SIGN-mediated viral attachment via glycan ligands is a potential broad-spectrum antiviral strategy.

Purpose of the Study:

• To evaluate polyvalent DC-SIGN ligands derived from oligomannose and complex-type glycans for antiviral applications.
• To investigate the thermodynamics of ligand-receptor interactions at mono- and multivalent levels.

Main Methods:

• Synthesis of polyvalent glycopolymers with specific carbohydrate epitopes (oligomannosides, α-l-Fuc) on a poly-l-lysine scaffold.
• Thermodynamic binding studies of ligands with the tetravalent DC-SIGN receptor.
• Cellular assays to assess inhibition of virus attachment and DC-SIGN-mediated dissemination.

Main Results:

• Glycopolymers demonstrated high potency in inhibiting DC-SIGN-mediated virus attachment (pico- to nanomolar range).
• Oligomannose epitopes exhibited significant activity.
• Polyvalent ligands showed effective inhibition of virus dissemination in cellular models.

Conclusions:

• Polyvalent DC-SIGN ligands, particularly those with oligomannose epitopes, are potent inhibitors of viral entry and dissemination.
• The biocompatible poly-l-lysine scaffold supports further preclinical development of these glycopolymers as broad-spectrum antivirals.