tetano
Editor, Senior Moderator
Commun Biol
. 2021 Apr 23;4(1):500.
doi: 10.1038/s42003-021-02029-w.
Structure and function analysis of a potent human neutralizing antibody CA521 [SUP]FALA[/SUP] against SARS-CoV-2
Deyong Song[SUP] #[/SUP][SUP] 1 [/SUP], Wenbo Wang[SUP] #[/SUP][SUP] 2 [/SUP], Chuangchuang Dong[SUP] 1 [/SUP], Zhenfei Ning[SUP] 1 [/SUP], Xiu Liu[SUP] 1 [/SUP], Chuan Liu[SUP] 3 [/SUP], Guangying Du[SUP] 4 [/SUP], Chunjie Sha[SUP] 4 [/SUP], Kailin Wang[SUP] 1 [/SUP], Jun Lu[SUP] 1 [/SUP], Baiping Sun[SUP] 1 [/SUP], Yanyan Zhao[SUP] 1 [/SUP], Qiaoping Wang[SUP] 1 [/SUP], Hongguang Xu[SUP] 1 [/SUP], Ying Li[SUP] 1 [/SUP], Zhenduo Shen[SUP] 1 [/SUP], Jie Jiao[SUP] 1 [/SUP], Ruiying Wang[SUP] 4 [/SUP], Jingwei Tian[SUP] 4 [/SUP], Wanhui Liu[SUP] 4 [/SUP], Lan Wang[SUP] 5 [/SUP], Yong-Qiang Deng[SUP] 6 [/SUP], Changlin Dou[SUP] 7 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521[SUP]FALA[/SUP], demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521[SUP]FALA[/SUP] showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521[SUP]FALA[/SUP] also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521[SUP]FALA[/SUP] inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521[SUP]FALA[/SUP] recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521[SUP]FALA[/SUP] blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions against COVID-19 and identifies CA521[SUP]FALA[/SUP] a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.
. 2021 Apr 23;4(1):500.
doi: 10.1038/s42003-021-02029-w.
Structure and function analysis of a potent human neutralizing antibody CA521 [SUP]FALA[/SUP] against SARS-CoV-2
Deyong Song[SUP] #[/SUP][SUP] 1 [/SUP], Wenbo Wang[SUP] #[/SUP][SUP] 2 [/SUP], Chuangchuang Dong[SUP] 1 [/SUP], Zhenfei Ning[SUP] 1 [/SUP], Xiu Liu[SUP] 1 [/SUP], Chuan Liu[SUP] 3 [/SUP], Guangying Du[SUP] 4 [/SUP], Chunjie Sha[SUP] 4 [/SUP], Kailin Wang[SUP] 1 [/SUP], Jun Lu[SUP] 1 [/SUP], Baiping Sun[SUP] 1 [/SUP], Yanyan Zhao[SUP] 1 [/SUP], Qiaoping Wang[SUP] 1 [/SUP], Hongguang Xu[SUP] 1 [/SUP], Ying Li[SUP] 1 [/SUP], Zhenduo Shen[SUP] 1 [/SUP], Jie Jiao[SUP] 1 [/SUP], Ruiying Wang[SUP] 4 [/SUP], Jingwei Tian[SUP] 4 [/SUP], Wanhui Liu[SUP] 4 [/SUP], Lan Wang[SUP] 5 [/SUP], Yong-Qiang Deng[SUP] 6 [/SUP], Changlin Dou[SUP] 7 [/SUP]
Affiliations
- PMID: 33893388
- DOI: 10.1038/s42003-021-02029-w
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521[SUP]FALA[/SUP], demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521[SUP]FALA[/SUP] showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521[SUP]FALA[/SUP] also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521[SUP]FALA[/SUP] inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521[SUP]FALA[/SUP] recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521[SUP]FALA[/SUP] blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions against COVID-19 and identifies CA521[SUP]FALA[/SUP] a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.