A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV

Yuan, Meng; Wu, Nicholas C.; Zhu, Xueyong; Lee, Chang-Chun D.; So, Ray T.  Y.; Lv, Huibin; Mok, Chris K.  P.; Wilson, Ian A.

doi:10.1126/science.abb7269

A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV

Journal Article · Fri Apr 03 00:00:00 EDT 2020 · Science

DOI:https://doi.org/10.1126/science.abb7269· OSTI ID:1629654

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The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology; DOE/OSTI
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology
Univ. of Hong Kong (Hong Kong). Li Ka Shing Faculty of Medince. School of Public Health. HKU-Pasteur Research Pole
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology; The Scripps Research Inst., La Jolla, CA (United States). The Skaggs Institute for Chemical Biology

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the “up” conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1629654

Alternate ID(s):: OSTI ID: 1630332

Journal Information:: Science, Journal Name: Science Journal Issue: 6491 Vol. 368; ISSN 0036-8075

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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