The search for a structural basis for therapeutic intervention against the SARS coronavirus

The 2003 outbreak of severe acute respiratory syndrome (SARS), caused by a previously unknown coronavirus called SARS-CoV, had profound social and economic impacts worldwide. Since then, structure-function studies of SARS-CoV proteins have provided a wealth of information that increases our understanding of the underlying mechanisms of SARS. While no effective therapy is currently available, considerable efforts have been made to develop vaccines and drugs to prevent SARS-CoV infection. In this review, some of the notable achievements made by SARS structural biology projects worldwide are examined and strategies for therapeutic intervention are discussed based on available SARS-CoV protein structures. To date, 12 structures have been determined by X-ray crystallography or NMR from the 28 proteins encoded by SARS-CoV. One key protein, the SARS-CoV main protease (M(pro)), has been the focus of considerable structure-based drug discovery efforts. This article highlights the importance of structural biology and shows that structures for drug design can be rapidly determined in the event of an emerging infectious disease.