The severe acute respiratory syndrome (SARS) virus belongs to the Coronaviridea family ofviruses. Its virion encodes several proteins including a replicase and four structural proteins. Here wedescribe the three-dimensional structure of the N-terminal domain of the SARS coronavirus (CoV)nucleocapsid protein. The protein consists of a five-stranded
sheet with a folding topology distinctfrom other RNA-binding proteins. Single-stranded RNAs bind to the protein surface at the junction betweena flexible, positively charged
hairpin and the core structure. NMR-based screening was used to identifylow molecular weight compounds that bind to this site.