Carbohydrate–protein interactions and multivalency: implications for the inhibition of influenza A virus infections

Abstract

Introduction: Protein-carbohydrate interactions play a very important role in many biological processes. A single interaction between a protein and a carbohydrate is usually weak, but multivalent ligands can compensate for this deficiency by binding multiple binding sites to one biological entity simultaneously. Over the past few years, numerous efforts have been made for the design and synthesis of carbohydrate-based multivalent ligands thereby serving as potent inhibitors for pathogens such as the influenza A virus. Areas covered: In this review, the authors cover a variety of multivalent systems from small to large molecules which showed a potent inhibitory effect against several pathogens. Expert opinion: Scaffold structure, linker type, and ligand density are important parameters that need to be optimized for potent multivalent inhibitors. The challenges of multivalent glycodrugs include issues such as bioavailability, pharmacokinetics, and immunogenicity which greatly depend on where the compounds are used in the body. Anti-flu (influenza) applications in the lungs using multivalent carbohydrates particularly has potential because of the high binding affinities. With much more research focusing on Influenza A virus inhibition, therapeutic applications may be achieved in the near future.

Stronger Together: Multivalent Phage Capsids Inhibit Virus Entry

“…Reversible carbohydrate‐receptor interactions have been widely implicated in many physiological and pathological processes, ranging from cell‐cell communication or tumor metastasis to viral infections [2,3] . Due to the usually weak interaction between a protein and a carbohydrate, typically a multivalent effect takes place.…”

The Symmetry of Viral Sialic Acid Binding Sites–Implications for Antiviral Strategies

“…Particularly the effects of the nature of the scaffold (or platform) and spatial sialic acid distribution in polyvalent viral attachment inhibitors are still being investigated [87]. Recently, excellent reviews covering the composition and biophysical properties of multivalent sialosides were published by Bhatia et al [88] and Lu et al [89], so we will not discuss this topic further here.…”

Surface Modification with Control over Ligand Density for the Study of Multivalent Biological Systems

“…[3] Pathogens, for example, take advantage of multiple proteinÀ carbohydrate interactions for cell adhesion which is the onset for the invasion or infection of the host cell. [4] One of the most studied multivalent systems is the influenza virus, which binds multivalently with its hemagglutinin (HA) protein to sialic acid residues expressed on the cell surface in the first stage of the infection ( Figure 1A). The cholera toxin (CT) secreted by Vibrio cholerae, composed of one toxic A subunit and five identical B subunits responsible of the uptake of the toxin, binds multivalently to GM1 residues of epithelial cells in the small intestine facilitating endocytosis ( Figure 1B).…”