The present invention provides crystalline forms of domain III of the West Nile Virus ("WNV") envelope protein in complex with a Fab fragment of a neutralizing antibody, methods of obtaining such crystals and high-resolution structures and atomic structure coordinates. The crystals of the invention and the atomic structural information are useful for solving crystal and solution structures of related and unrelated proteins, and for screening for, identifying or designing compounds or antibodies that bind to, modulate a biological activity of, or neutralize infection mediated by flaviviral envelope proteins.