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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/4595| A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein | |
| M. Gordon Joyce. Rajeshwer S Sankhala. Wei-Hung Chen. Misook Choe. Hongjun Bai. Agnes Hajduczki. Lianying Yan. Spencer L Sterling. Caroline Peterson. Ethan C Green. Clayton Smith. Natalia de Val. Mihret Amare. Paul Scott. Eric D Laing. Christopher C Broder. Morgane Rolland. Nelson L Michael. Kayvon Modjarrad. | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.1101/2020.03.15.992883 | |
| SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease--COVID-19-- within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronaviruss surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 [A]. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the "closed" prefusion S structure, but is accessible in "open" conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses. HIGHLIGHTSHigh resolution structure of the SARS-CoV-2 Receptor-Binding-Domain (RBD). Recognition of the SARS-CoV-2 RBD by SARS-CoV antibodies. Structure of the SARS-COV-2 RBD in complex with antibody CR3022. Identification of a cryptic site of vulnerability on the SARS-CoV-2 Spike. | |
| www.biorxiv.org | |
| 2020 | |
| Artículo | |
| https://www.biorxiv.org/content/10.1101/2020.03.15.992883v1.full.pdf | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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|---|---|---|---|
| 1106884.pdf | 3.65 MB | Adobe PDF | Visualizar/Abrir |