Multivalency effects in neuraminidase inhibitor design for influenza virus: This article is dedicated to Professor Horst Kunz on the occasion of his 80th birthday

Abstract

Multivalent interactions exist everywhere in nature. Here we will summarize the available data of multivalency effects that were explored for the design of novel neuraminidase (NA) inhibitors of influenza virus A. Although multivalency is a most effective tool to achieve high binding affinity, the molecular mechanisms are still poorly understood. The potency of multivalent neuraminidase inhibitors (NAIs) are dependent on the length, rigidity and chemical composition of the linker, ligand chemical structure and also the density of the ligand display. Important issues such as potential side-effects, drug-resistance, bioavailability and pharmacokinetics are largely unexplored with respect to application. The multivalent NAIs reported so far were of surprising potency and may play a role in therapeutic application and may prove valuable in forecasted pandemics.