A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV 2 Spike Glycoprotein

摘要: SARS-CoV-2 is a zoonotic virus that has caused pandemic of severe respiratory disease-COVID-19-within several months its initial identification. Comparable to the first SARS-CoV, this novel coronavirus's surface Spike (S) glycoprotein mediates cell entry via human ACE-2 receptor, and, thus, principal target for development vaccines and immunotherapeutics. Molecular information on S remains limited. Here we report crystal structure receptor-binding-domain (RBD) at highest resolution date, 1.95 A. We identified set SARS-reactive monoclonal antibodies with cross-reactivity RBD other betacoronavirus glycoproteins. One these antibodies, CR3022, was previously shown synergize binding site SARS-CoV reduce viral escape capacity. determined in complex RBD, defined broadly reactive epitope highly conserved across betacoronaviruses. This inaccessible "closed" prefusion structure, but accessible "open" conformations. first-ever antibody broad reactivity will allow antigenic assessment vaccine candidates, provide framework accelerated vaccine, immunotherapeutic diagnostic strategies against related