Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry

Ge，Jiwan1; Wang，Ruoke2; Ju，Bin3; Zhang，Qi2; Sun，Jing4; Chen，Peng2; Zhang，Senyan1; Tian，Yuling1; Shan，Sisi2; Cheng，Lin3; Zhou，Bing3; Song，Shuo3; Zhao，Juanjuan3; Wang，Haiyan3; Shi，Xuanling2; Ding，Qiang2; Liu，Lei3; Zhao，Jincun4; Zhang，Zheng3; Wang，Xinquan1; Zhang，Linqi2

2021-12-01

10.1038/s41467-020-20501-9

Nature Communications   影响因子和分区

2041-1723

2041-1723

Understanding the mechanism for antibody neutralization of SARS-CoV-2 is critical for the development of effective therapeutics and vaccines. We recently isolated a large number of monoclonal antibodies from SARS-CoV-2 infected individuals. Here we select the top three most potent yet variable neutralizing antibodies for in-depth structural and functional analyses. Crystal structural comparisons reveal differences in the angles of approach to the receptor binding domain (RBD), the size of the buried surface areas, and the key binding residues on the RBD of the viral spike glycoprotein. One antibody, P2C-1F11, most closely mimics binding of receptor ACE2, displays the most potent neutralizing activity in vitro and conferred strong protection against SARS-CoV-2 infection in Ad5-hACE2-sensitized mice. It also occupies the largest binding surface and demonstrates the highest binding affinity to RBD. More interestingly, P2C-1F11 triggers rapid and extensive shedding of S1 from the cell-surface expressed spike glycoprotein, with only minimal such effect by the remaining two antibodies. These results offer a structural and functional basis for potent neutralization via disruption of the very first and critical steps for SARS-CoV-2 cell entry.

SCI

英语

NI期刊

其他

Beijing Advanced Innovation Center for Structural Biology["2020YFC0848800","2020YFC0844200","2018ZX10731101-002","2017ZX10201101-001-003","2016YFD0500307"] ; National Key Plan for Scientific Research and Development of China["2020YFC0848800","2020YFC0844200","2018ZX10731101-002","2017ZX10201101-001-003","2016YFD0500307"] ; Science and Technology Innovation Committee of Shenzhen Municipality[202002073000002] ; Tsinghua University Initiative Scientific Research Program[20201080053] ; National Natural Science Foundation[81530065,91442127] ; Beijing Municipal Science and Technology Commission["171100000517-001","171100000517-003"] ; Tsinghua University Spring Breeze Fund[2020Z99CFG004] ; National Science Fund for Distinguished Young Scholars[82025022]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000670284400013

NATURE RESEARCH

2-s2.0-85099230064

Scopus

1.The Ministry of Education Key Laboratory of Protein Science,Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,Collaborative Innovation Center for Biotherapy,School of Life Sciences,Tsinghua University,Beijing,100084,China
2.Comprehensive AIDS Research Center,Beijing Advanced Innovation Center for Structural Biology,School of Medicine and Vanke School of Public Health,Tsinghua University,Beijing,100084,China
3.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People’s Hospital; The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,518112,China
4.State Key Laboratory of Respiratory Disease,National Clinical Research Center for Respiratory Disease,Guangzhou Institute of Respiratory Health,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou,510182,China

Ge，Jiwan,Wang，Ruoke,Ju，Bin,et al. Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry[J]. Nature Communications,2021,12(1).

Ge，Jiwan.,Wang，Ruoke.,Ju，Bin.,Zhang，Qi.,Sun，Jing.,...&Zhang，Linqi.(2021).Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry.Nature Communications,12(1).

Ge，Jiwan,et al."Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry".Nature Communications 12.1(2021).