A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2

被引：1003

作者：

Shi, Rui ^{[1
,2
]}

Shan, Chao ^{[3
]}

Duan, Xiaomin ^{[1
,2
]}

Chen, Zhihai ^{[4
]}

Liu, Peipei ^{[5
]}

Song, Jinwen ^{[6
]}

Song, Tao ^{[1
,7
,8
]}

Bi, Xiaoshan ^{[1
,9
]}

Han, Chao ^{[1
,2
]}

Wu, Lianao ^{[9
,10
]}

Gao, Ge ^{[3
]}

Hu, Xue ^{[3
]}

Zhang, Yanan ^{[3
]}

Tong, Zhou ^{[1
,10
]}

Huang, Weijin ^{[11
]}

Liu, William Jun ^{[5
]}

Wu, Guizhen ^{[5
]}

Zhang, Bo ^{[3
]}

Wang, Lan ^{[11
]}

Qi, Jianxun ^{[10
,12
]}

Feng, Hui ^{[13
]}

Wang, Fu-Sheng ^{[6
]}

Wang, Qihui ^{[1
,10
,12
]}

Gao, George Fu ^{[10
]}

Yuan, Zhiming ^{[3
]}

Yan, Jinghua ^{[1
,10
,12
]}

机构：

[1] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Microbial Physiol & Metab Engn, Beijing, Peoples R China

[2] Univ Chinese Acad Sci, Beijing, Peoples R China

[3] Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, Wuhan, Peoples R China

[4] Capital Med Univ, Beijing Ditan Hosp, Ctr Infect Dis, Beijing, Peoples R China

[5] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, NHC Key Lab Biosafety, Beijing, Peoples R China

[6] Peoples Liberat Army Gen Hosp, Natl Clin Res Ctr Infect Dis, Med Ctr 5, Treatment & Res Ctr Infect Dis, Beijing, Peoples R China

[7] Shanxi Acad Adv Res & Innovat, Taiyuan, Peoples R China

[8] Hebei Normal Univ Sci & Technol, Coll Anim Sci & Technol, Qinhuangdao, Hebei, Peoples R China

[9] Anhui Univ, Inst Phys Sci & Informat, Hefei, Peoples R China

[10] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China

[11] Natl Inst Food & Drug Control, Minist Hlth Res Qual & Standardizat Biotech Prod, Key Lab, Beijing, Peoples R China

[12] Univ Chinese Acad Sci, Savaid Med Sch, Beijing, Peoples R China

[13] Shanghai Junshi Biosci Co Ltd, Shanghai, Peoples R China

来源：

NATURE | 2020年 / 584卷 / 7819期

基金：

中国国家自然科学基金;

关键词：

SARS-COV; SPIKE PROTEIN; CORONAVIRUS; FEATURES;

D O I：

10.1038/s41586-020-2381-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

An outbreak of coronavirus disease 2019 (COVID-19)(1-3), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(4), has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic. Two monoclonal antibodies isolated from a patient with COVID-19 are shown to interfere with SARS-CoV-2-receptor binding, and one displays potent action against this virus in vitro and in a rhesus macaque model.

引用

页码：120 / +

页数：16

共 31 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution
Adams, Paul D.
Afonine, Pavel V.
Bunkoczi, Gabor
Chen, Vincent B.
Davis, Ian W.
Echols, Nathaniel
Headd, Jeffrey J.
Hung, Li-Wei
Kapral, Gary J.
Grosse-Kunstleve, Ralf W.
McCoy, Airlie J.
Moriarty, Nigel W.
Oeffner, Robert
Read, Randy J.
Richardson, David C.
Richardson, Jane S.
Terwilliger, Thomas C.
Zwart, Peter H.
[J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 : 213 - 221
[2] Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice
Channappanavar, Rudragouda
Fehr, Anthony R.
Vijay, Rahul
Mack, Matthias
Zhao, Jincun
Meyerholz, David K.
Perlman, Stanley
[J]. CELL HOST & MICROBE, 2016, 19 (02) : 181 - 193
[3] MolProbity: all-atom structure validation for macromolecular crystallography
Chen, Vincent B.
Arendall, W. Bryan, III
Headd, Jeffrey J.
Keedy, Daniel A.
Immormino, Robert M.
Kapral, Gary J.
Murray, Laura W.
Richardson, Jane S.
Richardson, David C.
[J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 : 12 - 21
[4] Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody
Corti, Davide
Misasi, John
Mulangu, Sabue
Stanley, Daphne A.
Kanekiyo, Masaru
Wollen, Suzanne
Ploquin, Aurelie
Doria-Rose, Nicole A.
Staupe, Ryan P.
Bailey, Michael
Shi, Wei
Choe, Misook
Marcus, Hadar
Thompson, Emily A.
Cagigi, Alberto
Silacci, Chiara
Fernandez-Rodriguez, Blanca
Perez, Laurent
Sallusto, Federica
Vanzetta, Fabrizia
Agatic, Gloria
Cameroni, Elisabetta
Kisalu, Neville
Gordon, Ingelise
Ledgerwood, Julie E.
Mascola, John R.
Graham, Barney S.
Muyembe-Tamfun, Jean-Jacques
Trefry, John C.
Lanzavecchia, Antonio
Sullivan, Nancy J.
[J]. SCIENCE, 2016, 351 (6279) : 1339 - 1342
[5] Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection
Du, Lanying
Zhang, Xiujuan
Liu, Jixiang
Jiang, Shibo
[J]. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2011, (51):
[6] The spike protein of SARS-CoV - a target for vaccine and therapeutic development
Du, Lanying
He, Yuxian
Zhou, Yusen
Liu, Shuwen
Zheng, Bo-Jian
Jiang, Shibo
[J]. NATURE REVIEWS MICROBIOLOGY, 2009, 7 (03) : 226 - 236
[7] Features and development of Coot
Emsley, P.
Lohkamp, B.
Scott, W. G.
Cowtan, K.
[J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2010, 66 : 486 - 501
[8] From "A'' IV to "Z''IKV: Attacks from Emerging and Re-emerging Pathogens
Gao, George F.
[J]. CELL, 2018, 172 (06) : 1157 - 1159
[9] Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study
Gaudinski, Martin R.
Coates, Emily E.
Novik, Laura
Widge, Alicia
Houser, Katherine V.
Burch, Eugeania
Holman, LaSonji A.
Gordon, Ingelise J.
Chen, Grace L.
Carter, Cristina
Nason, Martha
Sitar, Sandra
Yamshchikov, Galina
Berkowitz, Nina
Andrews, Charla
Vazquez, Sandra
Laurencot, Carolyn
Misasi, John
Arnold, Frank
Carlton, Kevin
Lawlor, Heather
Gall, Jason
Bailer, Robert T.
McDermott, Adrian
Capparelli, Edmund
Koup, Richard A.
Mascola, John R.
Graham, Barney S.
Sullivan, Nancy J.
Ledgerwood, Julie E.
[J]. LANCET, 2019, 393 (10174) : 889 - 898
[10] The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2
Gorbalenya, Alexander E.
Baker, Susan C.
Baric, Ralph S.
de Groot, Raoul J.
Drosten, Christian
Gulyaeva, Anastasia A.
Haagmans, Bart L.
Lauber, Chris
Leontovich, Andrey M.
Neuman, Benjamin W.
Penzar, Dmitry
Perlman, Stanley
Poon, Leo L. M.
Samborskiy, Dmitry V.
Sidorov, Igor A.
Sola, Isabel
Ziebuhr, John
[J]. NATURE MICROBIOLOGY, 2020, 5 (04) : 536 - 544

← 1 2 3 4 →