Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
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 th...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2020
|
| _version_ | 1797092913144922112 |
|---|---|
| author | Zhou, D Duyvesteyn, HME 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, RR Shah, PNM Tan, TK Rijal, P Donat, RF Godwin, K Buttigieg, KR Tree, JA Radecke, J Paterson, NG Supasa, P Mongkolsapaya, J Screaton, GR Carroll, MW Gilbert-Jaramillo, J Knight, ML James, W Owens, RJ Naismith, JH Townsend, AR Fry, EE Zhao, Y Ren, J Stuart, DI Huang, K-YA |
| author_facet | Zhou, D Duyvesteyn, HME 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, RR Shah, PNM Tan, TK Rijal, P Donat, RF Godwin, K Buttigieg, KR Tree, JA Radecke, J Paterson, NG Supasa, P Mongkolsapaya, J Screaton, GR Carroll, MW Gilbert-Jaramillo, J Knight, ML James, W Owens, RJ Naismith, JH Townsend, AR Fry, EE Zhao, Y Ren, J Stuart, DI Huang, K-YA |
| author_sort | Zhou, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:52:49Z |
| format | Journal article |
| id | oxford-uuid:c1dd09ce-81d4-41f5-b3f6-e8fa72ce2743 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:52:49Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:c1dd09ce-81d4-41f5-b3f6-e8fa72ce27432022-03-27T06:04:43ZStructural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patientJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c1dd09ce-81d4-41f5-b3f6-e8fa72ce2743EnglishSymplectic ElementsSpringer Nature 2020Zhou, DDuyvesteyn, HMEChen, C-PHuang, C-GChen, T-HShih, S-RLin, Y-CCheng, C-YCheng, S-HHuang, Y-CLin, T-YMa, CHuo, JCarrique, LMalinauskas, TRuza, RRShah, PNMTan, TKRijal, PDonat, RFGodwin, KButtigieg, KRTree, JARadecke, JPaterson, NGSupasa, PMongkolsapaya, JScreaton, GRCarroll, MWGilbert-Jaramillo, JKnight, MLJames, WOwens, RJNaismith, JHTownsend, ARFry, EEZhao, YRen, JStuart, DIHuang, K-YAThe 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. |
| spellingShingle | Zhou, D Duyvesteyn, HME 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, RR Shah, PNM Tan, TK Rijal, P Donat, RF Godwin, K Buttigieg, KR Tree, JA Radecke, J Paterson, NG Supasa, P Mongkolsapaya, J Screaton, GR Carroll, MW Gilbert-Jaramillo, J Knight, ML James, W Owens, RJ Naismith, JH Townsend, AR Fry, EE Zhao, Y Ren, J Stuart, DI Huang, K-YA Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient |
| title | Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient |
| title_full | Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient |
| title_fullStr | Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient |
| title_full_unstemmed | Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient |
| title_short | Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient |
| title_sort | structural basis for the neutralization of sars cov 2 by an antibody from a convalescent patient |
| work_keys_str_mv | AT zhoud structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT duyvesteynhme structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT chencp structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT huangcg structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT chenth structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT shihsr structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT linyc structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT chengcy structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT chengsh structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT huangyc structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT linty structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT mac structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT huoj structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT carriquel structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT malinauskast structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT ruzarr structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT shahpnm structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT tantk structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT rijalp structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT donatrf structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT godwink structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT buttigiegkr structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT treeja structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT radeckej structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT patersonng structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT supasap structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT mongkolsapayaj structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT screatongr structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT carrollmw structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT gilbertjaramilloj structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT knightml structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT jamesw structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT owensrj structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT naismithjh structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT townsendar structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT fryee structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT zhaoy structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT renj structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT stuartdi structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient AT huangkya structuralbasisfortheneutralizationofsarscov2byanantibodyfromaconvalescentpatient |