Virus-Glycan Interactions Studied by Solute NMR

The molecular mechanisms underlying viral cell entry remain poorly understood to date. Carbohydrates are structurally diverse and ubiquitous molecules that play a pivotal role in many biological processes, including viral infection via viral attachment to host cell glycoconjugates. Although crystallography and, more recently, cryo-electron microscopy (cryoEM) have yielded some spectacular results on these interactions, there is insufficient data available to elucidate the principles of virus-glycan recognition at atomic resolution. In recent years, nuclear magnetic resonance (NMR) has emerged as a key technique for studying virus-glycan interactions, offering a deeper understanding of the rules governing viral entry. Here, we provide an overview of the most relevant systems studied by solute NMR, including native viruses, virus-like particles (VLPs), and viral subparticles. Ligand-based NMR is exceptionally valuable for the study of native viruses and VLPs because it allows the determination of minimal structural requirements for glycan recognition under close to physiological conditions. Complementarily, protein NMR provides unique insights into protein-glycan binding, protein stability, and protein dynamics. Solute NMR has the potential to foster the development of innovative antiviral strategies that target the early phases of infection by interfering with viral host-cell glycan recognition.