Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

Daming Zhou; Helen M.E. Duyvesteyn; Cheng Pin Chen; Chung Guei Huang; Ting Hua Chen; Shin Ru Shih; Yi Chun Lin; Chien Yu Cheng; Shu Hsing Cheng; Yhu Chering Huang; Tzou Yien Lin; Che Ma; Jiandong Huo; Loic Carrique; Tomas Malinauskas; Reinis R. Ruza; Pranav N.M. Shah; Tiong Kit Tan; Pramila Rijal; Robert F. Donat; Kerry Godwin; Karen R. Buttigieg; Julia A. Tree; Julika Radecke; Neil G. Paterson; Piyada Supasa; Juthathip Mongkolsapaya; Gavin R. Screaton; Miles W. Carroll; Javier Gilbert-Jaramillo; Michael L. Knight; William James; Raymond J. Owens; James H. Naismith; Alain R. Townsend; Elizabeth E. Fry; Yuguang Zhao; Jingshan Ren; David I. Stuart; Kuan Ying A. Huang

doi:10.1038/s41594-020-0480-y

Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

Daming Zhou, Helen M.E. Duyvesteyn, Cheng Pin Chen, Chung Guei Huang, Ting Hua Chen, Shin Ru Shih, Yi Chun Lin, Chien Yu Cheng, Shu Hsing Cheng, Yhu Chering Huang, Tzou Yien Lin, Che Ma, Jiandong Huo, Loic Carrique, Tomas Malinauskas, Reinis R. Ruza, Pranav N.M. Shah, Tiong Kit Tan, Pramila Rijal, Robert F. DonatKerry Godwin, Karen R. Buttigieg, Julia A. Tree, Julika Radecke, Neil G. Paterson, Piyada Supasa, Juthathip Mongkolsapaya, Gavin R. Screaton, Miles W. Carroll, Javier Gilbert-Jaramillo, Michael L. Knight, William James, Raymond J. Owens, James H. Naismith, Alain R. Townsend, Elizabeth E. Fry, Yuguang Zhao, Jingshan Ren, David I. Stuart^*, Kuan Ying A. Huang^*

^*此作品的通信作者

研究成果: 期刊稿件 › 文章 › 同行評審

216 引文斯高帕斯（Scopus）

摘要

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 (K_D 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.

原文	英語
頁（從 - 到）	950-958
頁數	9
期刊	Nature Structural and Molecular Biology
卷	27
發行號	10
DOIs	https://doi.org/10.1038/s41594-020-0480-y
出版狀態	已出版 - 01 10 2020

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© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

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10.1038/s41594-020-0480-y

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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. Y. A. (2020). Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient. Nature Structural and Molecular Biology, 27(10), 950-958. https://doi.org/10.1038/s41594-020-0480-y

@article{c62c0ac8eada44f886ffdb29142aa54e,

title = "Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient",

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-{\AA}-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.",

author = "Daming Zhou and Duyvesteyn, {Helen M.E.} and Chen, {Cheng Pin} and Huang, {Chung Guei} and Chen, {Ting Hua} and Shih, {Shin Ru} and Lin, {Yi Chun} and Cheng, {Chien Yu} and Cheng, {Shu Hsing} and Huang, {Yhu Chering} and Lin, {Tzou Yien} and Che Ma and Jiandong Huo and Loic Carrique and Tomas Malinauskas and Ruza, {Reinis R.} and Shah, {Pranav N.M.} and Tan, {Tiong Kit} and Pramila Rijal and Donat, {Robert F.} and Kerry Godwin and Buttigieg, {Karen R.} and Tree, {Julia A.} and Julika Radecke and Paterson, {Neil G.} and Piyada Supasa and Juthathip Mongkolsapaya and Screaton, {Gavin R.} and Carroll, {Miles W.} and Javier Gilbert-Jaramillo and Knight, {Michael L.} and William James and Owens, {Raymond J.} and Naismith, {James H.} and Townsend, {Alain R.} and Fry, {Elizabeth E.} and Yuguang Zhao and Jingshan Ren and Stuart, {David I.} and Huang, {Kuan Ying A.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2020",

month = oct,

day = "1",

doi = "10.1038/s41594-020-0480-y",

language = "英语",

volume = "27",

pages = "950--958",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "Nature Research",

number = "10",

}

Zhou, D, Duyvesteyn, HME, Chen, CP, Huang, CG, Chen, TH, Shih, SR, Lin, YC, Cheng, CY, Cheng, SH, Huang, YC, Lin, TY, 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, KYA 2020, 'Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient', Nature Structural and Molecular Biology, 卷 27, 編號 10, 頁 950-958. https://doi.org/10.1038/s41594-020-0480-y

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.

PY - 2020/10/1

Y1 - 2020/10/1

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.

AB - 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.

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U2 - 10.1038/s41594-020-0480-y

DO - 10.1038/s41594-020-0480-y

M3 - 文章

C2 - 32737466

AN - SCOPUS:85088842557

SN - 1545-9993

VL - 27

SP - 950

EP - 958

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 10

ER -

Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

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