Molecular recognition of ligands by native viruses and virus-like particles as studied by NMR experiments

Viral entry into host cells is a process that in the majority of cases is not understood in its molecular details. The first step of viral entry is the recognition of cellular receptors on host cells by viruses, and although X-ray crystallography had yielded some spectacular results in individual cases, in general there is little data available to unravel the principles of virus-ligand recognition at atomic resolution. Therefore, new techniques that uncover the molecular details of these recognition processes are needed. The investigation of virus-ligand interactions using ligand-based NMR techniques is an emerging field with the potential to substantially contribute to a deeper understanding of the molecular aspects of viral entry into host cells. Here, we give an overview that covers some of the systems studied so far. This comprises native viruses as well as virus-like particles (VLPs). We will not address studies that have been performed with individual proteins that are not in a native environment. It turns out that STD NMR in particular has a great potential to shine light on the viral entry process as this technique requires only very moderate amounts of viruses or VLPs and corresponding ligands. As a further advantage, this approach is also applicable to ligands that bind to viruses with medium to low affinity. Therefore, STD NMR is extremely well suited for development of antiviral entry inhibitors utilizing fragment-based approaches with low molecular weight compounds.