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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.
Affiliation
  • M. Gordon Joyce; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Rajeshwer S Sankhala; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA
  • Wei-Hung Chen; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Misook Choe; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Hongjun Bai; MHRP, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Agnes Hajduczki; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Lianying Yan; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA, Bethesda, MD, USA
  • Spencer L Sterling; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA, Bethesda, MD, USA
  • Caroline Peterson; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Ethan C Green; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA, Bethesda, MD, USA.
  • Clayton Smith; Center for Cancer Research (CCR), National Cancer Institute (NCI)
  • Natalia de Val; Center for Cancer Research (CCR), National Cancer Institute (NCI)
  • Mihret Amare; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Paul Scott; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Eric D Laing; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA, Bethesda, MD, USA.
  • Christopher C Broder; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA, Bethesda, MD, USA.
  • Morgane Rolland; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Nelson L Michael; Walter Reed Army Institute of Research
  • Kayvon Modjarrad; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Preprint in English | bioRxiv | ID: ppbiorxiv-992883
ABSTRACT
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.
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Rct Language: English Year: 2020 Document type: Preprint
Fulltext
Add to My VHL
Print
XML
Search on Google
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Rct Language: English Year: 2020 Document type: Preprint