Structural Biology of Noroviruses

Noroviruses constitute a major genus in the family Caliciviridae, which contains icosahedral viruses with positive-sense single-stranded RNA genome. In humans, these constantly evolving viruses are the cause of sporadic and epidemic gastroenteritis. Despite a lack of a reproducible cell culture system or a small animal model, remarkable progress has been made in our understanding of the molecular biology, immunology, structural biology, and evolution of human noroviruses. This understanding is further enhanced by studies of nonhuman noroviruses and animal caliciviruses that are cultivatable. The main focus of this chapter is to review our current understanding of the structural biology of noroviruses in particular and of caliciviruses in general, with an emphasis on the unique modular organization of the capsid that allows for strain-dependent variations in glycan recognition and antigenicity to facilitate sustained virus evolution. Finally, structures of the proteins are reviewed that are critical for virus replication and that can be targeted in the design of small molecule drugs for use as effective antivirals.