Structural Basis of Neutralization by a Human Anti-severe Acute Respiratory Syndrome Spike Protein Antibody, 80R

Abstract

Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.

Cited by papers we hold 12

• Different Cases of SARS-CoV-2 Infection and Its Impact on Health and Economy with Special Emphasis on Antiviral Drug Targets · 2020
  Not checked
• Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies · 2020
  No notice
• Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike · 2020
  Corrected
• Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition · 2020
  No notice
• Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies · 2020
  No notice
• A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction · 2020
  No notice
• Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions · 2020
  No notice
• A panel of human neutralizing mAbs targeting SARS-CoV-2 spike at multiple epitopes · 2020
  No notice
• A new coronavirus associated with human respiratory disease in China · 2020
  Corrected
• A human monoclonal antibody blocking SARS-CoV-2 infection · 2020
  Corrected
• Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody · 2020
  No notice
• Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding · 2020
  No notice

Questions about this paper

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.