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Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient.
Nat Struct Mol Biol. 2020 10; 27(10):950-958.NS

Abstract

The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD-EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19.

Authors+Show Affiliations

Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, and National Yang-Ming University, Taipei, Taiwan.Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.Genomics Research Center, Academia Sinica, Taipei, Taiwan.Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, and Taipei Medical University, Taipei, Taiwan.Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, and National Yang-Ming University, Taipei, Taiwan.Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, and Taipei Medical University, Taipei, Taiwan.Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.Genomics Research Center, Academia Sinica, Taipei, Taiwan.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK. The Rosalind Franklin Institute, Harwell Campus, Didcot, UK. Protein Production UK, Research Complex at Harwell, Harwell Science & Innovation Campus, Didcot, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK.MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.National Infection Service, Public Health England, Porton Down, Salisbury, UK.National Infection Service, Public Health England, Porton Down, Salisbury, UK.National Infection Service, Public Health England, Porton Down, Salisbury, UK.Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK.Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.National Infection Service, Public Health England, Porton Down, Salisbury, UK. Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.William Dunn School of Pathology, University of Oxford, Oxford, UK.William Dunn School of Pathology, University of Oxford, Oxford, UK.William Dunn School of Pathology, University of Oxford, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK. The Rosalind Franklin Institute, Harwell Campus, Didcot, UK. Protein Production UK, Research Complex at Harwell, Harwell Science & Innovation Campus, Didcot, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK. The Rosalind Franklin Institute, Harwell Campus, Didcot, UK. Protein Production UK, Research Complex at Harwell, Harwell Science & Innovation Campus, Didcot, UK.MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK. dave@strubi.ox.ac.uk. Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK. dave@strubi.ox.ac.uk. Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK. dave@strubi.ox.ac.uk.Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan. arthur1726@cgmh.org.tw. Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan. arthur1726@cgmh.org.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32737466

Citation

Zhou, Daming, et al. "Structural Basis for the Neutralization of SARS-CoV-2 By an Antibody From a Convalescent Patient." Nature Structural & Molecular Biology, vol. 27, no. 10, 2020, pp. 950-958.
Zhou D, Duyvesteyn HME, Chen CP, et al. Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient. Nat Struct Mol Biol. 2020;27(10):950-958.
Zhou, D., Duyvesteyn, H. M. E., Chen, C. P., Huang, C. G., Chen, T. H., Shih, S. R., Lin, Y. C., Cheng, C. Y., Cheng, S. H., Huang, Y. C., Lin, T. Y., Ma, C., Huo, J., Carrique, L., Malinauskas, T., Ruza, R. R., Shah, P. N. M., Tan, T. K., Rijal, P., ... Huang, K. A. (2020). Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient. Nature Structural & Molecular Biology, 27(10), 950-958. https://doi.org/10.1038/s41594-020-0480-y
Zhou D, et al. Structural Basis for the Neutralization of SARS-CoV-2 By an Antibody From a Convalescent Patient. Nat Struct Mol Biol. 2020;27(10):950-958. PubMed PMID: 32737466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient. AU - Zhou,Daming, AU - Duyvesteyn,Helen M E, AU - Chen,Cheng-Pin, AU - Huang,Chung-Guei, AU - Chen,Ting-Hua, AU - Shih,Shin-Ru, AU - Lin,Yi-Chun, AU - Cheng,Chien-Yu, AU - Cheng,Shu-Hsing, AU - Huang,Yhu-Chering, AU - Lin,Tzou-Yien, AU - Ma,Che, AU - Huo,Jiandong, AU - Carrique,Loic, AU - Malinauskas,Tomas, AU - Ruza,Reinis R, AU - Shah,Pranav N M, AU - Tan,Tiong Kit, AU - Rijal,Pramila, AU - Donat,Robert F, AU - Godwin,Kerry, AU - Buttigieg,Karen R, AU - Tree,Julia A, AU - Radecke,Julika, AU - Paterson,Neil G, AU - Supasa,Piyada, AU - Mongkolsapaya,Juthathip, AU - Screaton,Gavin R, AU - Carroll,Miles W, AU - Gilbert-Jaramillo,Javier, AU - Knight,Michael L, AU - James,William, AU - Owens,Raymond J, AU - Naismith,James H, AU - Townsend,Alain R, AU - Fry,Elizabeth E, AU - Zhao,Yuguang, AU - Ren,Jingshan, AU - Stuart,David I, AU - Huang,Kuan-Ying A, Y1 - 2020/07/31/ PY - 2020/06/07/received PY - 2020/07/10/accepted PY - 2020/8/2/pubmed PY - 2020/10/30/medline PY - 2020/8/2/entrez SP - 950 EP - 958 JF - Nature structural & molecular biology JO - Nat Struct Mol Biol VL - 27 IS - 10 N2 - The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD-EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19. SN - 1545-9985 UR - https://www.unboundmedicine.com/medline/citation/32737466/Structural_basis_for_the_neutralization_of_SARS_CoV_2_by_an_antibody_from_a_convalescent_patient_ L2 - https://doi.org/10.1038/s41594-020-0480-y DB - PRIME DP - Unbound Medicine ER -