tetano
Editor, Senior Moderator
Nature
. 2020 May 26.
doi: 10.1038/s41586-020-2380-z. Online ahead of print.
Human Neutralizing Antibodies Elicited by SARS-CoV-2 Infection
Bin Ju[SUP] 1 2 [/SUP], Qi Zhang[SUP] 3 [/SUP], Jiwan Ge[SUP] 4 [/SUP], Ruoke Wang[SUP] 3 [/SUP], Jing Sun[SUP] 5 [/SUP], Xiangyang Ge[SUP] 1 [/SUP], Jiazhen Yu[SUP] 1 [/SUP], Sisi Shan[SUP] 3 [/SUP], Bing Zhou[SUP] 1 [/SUP], Shuo Song[SUP] 1 [/SUP], Xian Tang[SUP] 1 [/SUP], Jinfang Yu[SUP] 4 [/SUP], Jun Lan[SUP] 4 [/SUP], Jing Yuan[SUP] 6 [/SUP], Haiyan Wang[SUP] 1 [/SUP], Juanjuan Zhao[SUP] 1 2 [/SUP], Shuye Zhang[SUP] 7 [/SUP], Youchun Wang[SUP] 8 [/SUP], Xuanling Shi[SUP] 3 [/SUP], Lei Liu[SUP] 1 2 [/SUP], Jincun Zhao[SUP] 5 [/SUP], Xinquan Wang[SUP] 9 [/SUP], Zheng Zhang[SUP] 10 11 [/SUP], Linqi Zhang[SUP] 12 [/SUP]
Affiliations
Abstract
The emerging coronavirus SARS-CoV-2 pandemic presents a global health emergency in urgent need of interventions[SUP]1-3[/SUP]. SARS-CoV-2 entry into the target cells depends on binding between the receptor-binding domain (RBD) of the viral Spike protein and the ACE2 cell receptor[SUP]2,4-6[/SUP]. Here, we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells of eight SARS-CoV-2 infected individuals. We identified antibodies with potent anti-SARS-CoV-2 neutralization activity that correlates with their competitive capacity with ACE2 for RBD binding. Surprisingly, neither the anti-SARS-CoV-2 antibodies nor the infected plasma cross-reacted with SARS-CoV or MERS-CoV RBDs, although substantial plasma cross-reactivity to their trimeric Spike proteins was found. Crystal structure analysis of RBD-bound antibody revealed steric hindrance that inhibits viral engagement with ACE2 and thereby blocks viral entry. These findings suggest that anti-RBD antibodies are viral species-specific inhibitors. The antibodies identified here may be candidates for the development of SARS-CoV-2 clinical interventions.
. 2020 May 26.
doi: 10.1038/s41586-020-2380-z. Online ahead of print.
Human Neutralizing Antibodies Elicited by SARS-CoV-2 Infection
Bin Ju[SUP] 1 2 [/SUP], Qi Zhang[SUP] 3 [/SUP], Jiwan Ge[SUP] 4 [/SUP], Ruoke Wang[SUP] 3 [/SUP], Jing Sun[SUP] 5 [/SUP], Xiangyang Ge[SUP] 1 [/SUP], Jiazhen Yu[SUP] 1 [/SUP], Sisi Shan[SUP] 3 [/SUP], Bing Zhou[SUP] 1 [/SUP], Shuo Song[SUP] 1 [/SUP], Xian Tang[SUP] 1 [/SUP], Jinfang Yu[SUP] 4 [/SUP], Jun Lan[SUP] 4 [/SUP], Jing Yuan[SUP] 6 [/SUP], Haiyan Wang[SUP] 1 [/SUP], Juanjuan Zhao[SUP] 1 2 [/SUP], Shuye Zhang[SUP] 7 [/SUP], Youchun Wang[SUP] 8 [/SUP], Xuanling Shi[SUP] 3 [/SUP], Lei Liu[SUP] 1 2 [/SUP], Jincun Zhao[SUP] 5 [/SUP], Xinquan Wang[SUP] 9 [/SUP], Zheng Zhang[SUP] 10 11 [/SUP], Linqi Zhang[SUP] 12 [/SUP]
Affiliations
- PMID: 32454513
- DOI: 10.1038/s41586-020-2380-z
Abstract
The emerging coronavirus SARS-CoV-2 pandemic presents a global health emergency in urgent need of interventions[SUP]1-3[/SUP]. SARS-CoV-2 entry into the target cells depends on binding between the receptor-binding domain (RBD) of the viral Spike protein and the ACE2 cell receptor[SUP]2,4-6[/SUP]. Here, we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells of eight SARS-CoV-2 infected individuals. We identified antibodies with potent anti-SARS-CoV-2 neutralization activity that correlates with their competitive capacity with ACE2 for RBD binding. Surprisingly, neither the anti-SARS-CoV-2 antibodies nor the infected plasma cross-reacted with SARS-CoV or MERS-CoV RBDs, although substantial plasma cross-reactivity to their trimeric Spike proteins was found. Crystal structure analysis of RBD-bound antibody revealed steric hindrance that inhibits viral engagement with ACE2 and thereby blocks viral entry. These findings suggest that anti-RBD antibodies are viral species-specific inhibitors. The antibodies identified here may be candidates for the development of SARS-CoV-2 clinical interventions.