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.

KEYWORDS:

• Carbohydrate-protein interactions
• influenza A virus
• hemagglutinin
• multivalent inhibitors

Article highlights

• Carbohydrate-protein interactions are involved in many processes including those that cause disease.

• Multivalency in the design of inhibitors can dramatically increase inhibitory potencies.

• Multivalent carbohydrates haven been demonstrated effective in selected animal models and have progressed in one case to clinical trials.

• The hemagglutinin (HA) protein of Influenza virus A is an important and challenging target protein.

• Multivalency approaches are starting to become successful in addressing HA.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

W Liu is financially supported by a scholarship from the China Scholarship Council (CSC) file no. 201306300064.