Structural basis of a shared antibody response to SARS-CoV-2

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Molecular understanding of neutralizing antibody responses to SARS-CoV-2 could accelerate vaccine design and drug discovery. We analyzed 294 anti-SARS-CoV-2 antibodies and found that IGHV3-53 is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53 neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33 to 3.20 Å resolution revealed that the germline-encoded residues dominate recognition of the ACE2 binding site. This binding mode limits the IGHV3-53 antibodies to short CDR H3 loops, but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate design of antigens that elicit this type of neutralizing response.

Related collections

Most cited references 29

Record: found
Abstract: found
Article: found

Is Open Access

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

0 comments Cited 10186 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett … (2020)

Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260

0 comments Cited 4192 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Jun Lan, Jiwan Ge, Jinfang Yu … (2020)

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.

0 comments Cited 2929 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Science

Journal ID (iso-abbrev): Science

Journal ID (publisher-id): SCIENCE

Title: Science (New York, N.y.)

Publisher: American Association for the Advancement of Science

ISSN (Print): 0036-8075

ISSN (Electronic): 1095-9203

Publication date (Electronic): 13 July 2020

Electronic Location Identifier: eabd2321

Affiliations

[1 ]Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

[2 ]Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

[3 ]IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.

[4 ]Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

[5 ]Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.

[6 ]IAVI, New York, NY10004, USA.

[7 ]Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.

[8 ]The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.

Author notes

[*]

These authors contributed equally to this work.

[† ]Corresponding author. Email: wilson@ 123456scripps.edu

Author information

Meng Yuan https://orcid.org/0000-0001-9754-4503

Hejun Liu https://orcid.org/0000-0002-2412-7853

Nicholas C. Wu https://orcid.org/0000-0002-9078-6697

Chang-Chun D. Lee https://orcid.org/0000-0002-5470-2484

Xueyong Zhu https://orcid.org/0000-0002-6021-3740

Fangzhu Zhao https://orcid.org/0000-0002-3172-1340

Deli Huang https://orcid.org/0000-0002-6989-639X

Wenli Yu https://orcid.org/0000-0002-4025-2646

Henry Tien https://orcid.org/0000-0001-7584-5989

Thomas F. Rogers https://orcid.org/0000-0001-9756-327X

Elise Landais https://orcid.org/0000-0002-8183-5565

Devin Sok https://orcid.org/0000-0002-9354-1740

Joseph G. Jardine https://orcid.org/0000-0001-8951-1074

Dennis R. Burton https://orcid.org/0000-0001-6711-9864

Ian A. Wilson https://orcid.org/0000-0002-6469-2419

Article

Publisher ID: abd2321

DOI: 10.1126/science.abd2321

PMC ID: 7402627

PubMed ID: 32661058

SO-VID: 247a72d0-731c-4451-b85d-07bdf7d4960b

Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 09 June 2020

Date accepted : 07 July 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: K99 AI139445

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: UM1 AI44462

Funded by: doi http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;

Structural basis of a shared antibody response to SARS-CoV-2

Read this article at

Abstract

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 29

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Comments

Comment on this article

Similar content 516

Cited by 289