tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2022 Apr 5;7(1):114.
doi: 10.1038/s41392-022-00954-8.
A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD
Xiaofei Wang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Ao Hu[SUP] #[/SUP][SUP] 1 [/SUP], Xiangyu Chen[SUP] #[/SUP][SUP] 4 5 [/SUP], Yixin Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Fei Yu[SUP] #[/SUP][SUP] 1 6 [/SUP], Shuai Yue[SUP] 7 [/SUP], Arong Li[SUP] 2 3 [/SUP], Junsong Zhang[SUP] 1 6 [/SUP], Zhiwei Pan[SUP] 7 [/SUP], Yang Yang[SUP] 7 [/SUP], Yao Lin[SUP] 7 [/SUP], Leiqiong Gao[SUP] 7 [/SUP], Jing Zhou[SUP] 7 [/SUP], Jing Zhao[SUP] 8 [/SUP], Fang Li[SUP] 9 10 [/SUP], Yaling Shi[SUP] 9 [/SUP], Feng Huang[SUP] 1 6 [/SUP], Xiaofan Yang[SUP] 1 [/SUP], Yi Peng[SUP] 1 [/SUP], Luoyang Tu[SUP] 1 [/SUP], Huan Zhang[SUP] 11 [/SUP], Huanying Zheng[SUP] 11 [/SUP], Jun He[SUP] 12 [/SUP], Hui Zhang[SUP] 1 [/SUP], Lifan Xu[SUP] 7 [/SUP], Qizhao Huang[SUP] 4 [/SUP], Yongqun Zhu[SUP] 13 14 [/SUP], Kai Deng[SUP] 15 [/SUP], Lilin Ye[SUP] 16 [/SUP]
Affiliations
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.
. 2022 Apr 5;7(1):114.
doi: 10.1038/s41392-022-00954-8.
A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD
Xiaofei Wang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Ao Hu[SUP] #[/SUP][SUP] 1 [/SUP], Xiangyu Chen[SUP] #[/SUP][SUP] 4 5 [/SUP], Yixin Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Fei Yu[SUP] #[/SUP][SUP] 1 6 [/SUP], Shuai Yue[SUP] 7 [/SUP], Arong Li[SUP] 2 3 [/SUP], Junsong Zhang[SUP] 1 6 [/SUP], Zhiwei Pan[SUP] 7 [/SUP], Yang Yang[SUP] 7 [/SUP], Yao Lin[SUP] 7 [/SUP], Leiqiong Gao[SUP] 7 [/SUP], Jing Zhou[SUP] 7 [/SUP], Jing Zhao[SUP] 8 [/SUP], Fang Li[SUP] 9 10 [/SUP], Yaling Shi[SUP] 9 [/SUP], Feng Huang[SUP] 1 6 [/SUP], Xiaofan Yang[SUP] 1 [/SUP], Yi Peng[SUP] 1 [/SUP], Luoyang Tu[SUP] 1 [/SUP], Huan Zhang[SUP] 11 [/SUP], Huanying Zheng[SUP] 11 [/SUP], Jun He[SUP] 12 [/SUP], Hui Zhang[SUP] 1 [/SUP], Lifan Xu[SUP] 7 [/SUP], Qizhao Huang[SUP] 4 [/SUP], Yongqun Zhu[SUP] 13 14 [/SUP], Kai Deng[SUP] 15 [/SUP], Lilin Ye[SUP] 16 [/SUP]
Affiliations
- PMID: 35383141
- DOI: 10.1038/s41392-022-00954-8
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.