Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-20501-9
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Funding
- 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]
- Tencent Foundation
- Shuidi Foundation
- TH Capital
- National Science Fund for Distinguished Young Scholars [82025022]
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The authors compare the crystal structures and investigate the neutralization mechanisms of three neutralizing antibodies against SARS-CoV-2 and find that one antibody, P2C-1F11, closely mimics binding of receptor ACE2 and displays the most potent neutralizing activity in vitro, as well as conferring protection against SARS-CoV-2 infection in Ad5-hACE2-sensitized mice.
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. Here, the authors compare the crystal structures and investigate the neutralization mechanisms of three neutralizing antibodies against SARS-CoV-2 and find that one antibody, P2C-1F11, closely mimics binding of receptor ACE2 and displays the most potent neutralizing activity in vitro, as well as conferring protection against SARS-CoV-2 infection in Ad5-hACE2-sensitized mice.
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