Your browser doesn't support javascript.
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike.
Huo, Jiandong; Zhao, Yuguang; Ren, Jingshan; Zhou, Daming; Duyvesteyn, Helen M E; Ginn, Helen M; Carrique, Loic; Malinauskas, Tomas; Ruza, Reinis R; Shah, Pranav N M; Tan, Tiong Kit; Rijal, Pramila; Coombes, Naomi; Bewley, Kevin R; Tree, Julia A; Radecke, Julika; Paterson, Neil G; Supasa, Piyada; Mongkolsapaya, Juthathip; Screaton, Gavin R; Carroll, Miles; Townsend, Alain; Fry, Elizabeth E; Owens, Raymond J; Stuart, David I.
  • Huo J; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK; The Rosalind Franklin Institute, Harwell Campus, OX11 0FA, UK; Protein Production UK, Research Complex at Harwell, Harwell Science & Innovation Campus, Didcot, OX11 0FA,
  • Zhao Y; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK.
  • Ren J; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK. Electronic address: ren@strubi.ox.ac.uk.
  • Zhou D; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK.
  • Duyvesteyn HME; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK.
  • Ginn HM; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, OX11 0DE, UK.
  • Carrique L; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK.
  • Malinauskas T; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK.
  • Ruza RR; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK.
  • Shah PNM; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK.
  • Tan TK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
  • Rijal P; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK; Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7FZ, UK.
  • Coombes N; National Infection Service, Public Health England, Porton Down, Salisbury, SP4 0JG, UK.
  • Bewley KR; National Infection Service, Public Health England, Porton Down, Salisbury, SP4 0JG, UK.
  • Tree JA; National Infection Service, Public Health England, Porton Down, Salisbury, SP4 0JG, UK.
  • Radecke J; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, OX11 0DE, UK.
  • Paterson NG; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, OX11 0DE, UK.
  • Supasa P; Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
  • Mongkolsapaya J; Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK; Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 73170, Thailand.
  • Screaton GR; Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
  • Carroll M; National Infection Service, Public Health England, Porton Down, Salisbury, SP4 0JG, UK; Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
  • Townsend A; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK; Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7FZ, UK.
  • Fry EE; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK.
  • Owens RJ; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK; The Rosalind Franklin Institute, Harwell Campus, OX11 0FA, UK; Protein Production UK, Research Complex at Harwell, Harwell Science & Innovation Campus, Didcot, OX11 0FA,
  • Stuart DI; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, OX11 0DE, UK; Instruct-ERIC, Oxford House, Parkway Court, John Smith Drive, Oxford, OX4 2JY, UK. E
Cell Host Microbe ; 28(3): 445-454.e6, 2020 09 09.
Article in English | MEDLINE | ID: covidwho-615004
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / Betacoronavirus / Antibodies, Viral Topics: Vaccines Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2020 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / Betacoronavirus / Antibodies, Viral Topics: Vaccines Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2020 Document Type: Article