tetano
Editor, Senior Moderator
Nat Commun
. 2021 Jan 11;12(1):264.
doi: 10.1038/s41467-020-20465-w.
Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections
Chao Zhang[SUP] 1 [/SUP], Yifan Wang[SUP] 2 [/SUP], Yuanfei Zhu[SUP] 3 [/SUP], Caixuan Liu[SUP] 2 [/SUP], Chenjian Gu[SUP] 3 [/SUP], Shiqi Xu[SUP] 1 [/SUP], Yalei Wang[SUP] 1 [/SUP], Yu Zhou[SUP] 1 [/SUP], Yanxing Wang[SUP] 2 4 [/SUP], Wenyu Han[SUP] 2 [/SUP], Xiaoyu Hong[SUP] 2 [/SUP], Yong Yang[SUP] 1 [/SUP], Xueyang Zhang[SUP] 1 [/SUP], Tingfeng Wang[SUP] 1 [/SUP], Cong Xu[SUP] 2 [/SUP], Qin Hong[SUP] 2 [/SUP], Shutian Wang[SUP] 2 [/SUP], Qiaoyu Zhao[SUP] 2 [/SUP], Weihua Qiao[SUP] 1 [/SUP], Jinkai Zang[SUP] 1 [/SUP], Liangliang Kong[SUP] 5 [/SUP], Fangfang Wang[SUP] 5 [/SUP], Haikun Wang[SUP] 1 [/SUP], Di Qu[SUP] 3 6 [/SUP], Dimitri Lavillette[SUP] 1 [/SUP], Hong Tang[SUP] 1 [/SUP], Qiang Deng[SUP] 7 [/SUP], Youhua Xie[SUP] 8 [/SUP], Yao Cong[SUP] 9 10 [/SUP], Zhong Huang[SUP] 11 [/SUP]
Affiliations
Abstract
The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 ? resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.
. 2021 Jan 11;12(1):264.
doi: 10.1038/s41467-020-20465-w.
Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections
Chao Zhang[SUP] 1 [/SUP], Yifan Wang[SUP] 2 [/SUP], Yuanfei Zhu[SUP] 3 [/SUP], Caixuan Liu[SUP] 2 [/SUP], Chenjian Gu[SUP] 3 [/SUP], Shiqi Xu[SUP] 1 [/SUP], Yalei Wang[SUP] 1 [/SUP], Yu Zhou[SUP] 1 [/SUP], Yanxing Wang[SUP] 2 4 [/SUP], Wenyu Han[SUP] 2 [/SUP], Xiaoyu Hong[SUP] 2 [/SUP], Yong Yang[SUP] 1 [/SUP], Xueyang Zhang[SUP] 1 [/SUP], Tingfeng Wang[SUP] 1 [/SUP], Cong Xu[SUP] 2 [/SUP], Qin Hong[SUP] 2 [/SUP], Shutian Wang[SUP] 2 [/SUP], Qiaoyu Zhao[SUP] 2 [/SUP], Weihua Qiao[SUP] 1 [/SUP], Jinkai Zang[SUP] 1 [/SUP], Liangliang Kong[SUP] 5 [/SUP], Fangfang Wang[SUP] 5 [/SUP], Haikun Wang[SUP] 1 [/SUP], Di Qu[SUP] 3 6 [/SUP], Dimitri Lavillette[SUP] 1 [/SUP], Hong Tang[SUP] 1 [/SUP], Qiang Deng[SUP] 7 [/SUP], Youhua Xie[SUP] 8 [/SUP], Yao Cong[SUP] 9 10 [/SUP], Zhong Huang[SUP] 11 [/SUP]
Affiliations
- PMID: 33431876
- DOI: 10.1038/s41467-020-20465-w
Abstract
The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 ? resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.