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TitleStructure and function analysis of a potent human neutralizing antibody CA521 against SARS-CoV-2.
Journal, issue, pagesCommun Biol, Vol. 4, Issue 1, Page 500, Year 2021
Publish dateApr 23, 2021
AuthorsDeyong Song / Wenbo Wang / Chuangchuang Dong / Zhenfei Ning / Xiu Liu / Chuan Liu / Guangying Du / Chunjie Sha / Kailin Wang / Jun Lu / Baiping Sun / Yanyan Zhao / Qiaoping Wang / Hongguang Xu / Ying Li / Zhenduo Shen / Jie Jiao / Ruiying Wang / Jingwei Tian / Wanhui Liu / Lan Wang / Yong-Qiang Deng / Changlin Dou /
PubMed AbstractSevere 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 ...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, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521 showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521 also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521 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 recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521 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 a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.
External linksCommun Biol / PubMed:33893388 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 4.1 Å
Structure data

EMDB-30628:
SARS-CoV-2 spike in complex with the CA521 neutralizing antibody (focused map)
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-30629:
SARS-CoV-2 spike in complex with the CA521 neutralizing antibody (consensus map)
Method: EM (single particle) / Resolution: 3.8 Å

30950

7e23

EMDB-30950, PDB-7e23:
SARS-CoV-2 spike in complex with the CA521 neutralizing antibody Fab (focused refinement on Fab-RBD)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-30951:
SARS-CoV-2 spike in complex with the CA521 neutralizing antibody Fab (consensus map)
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Spike / SARS-CoV-2 / Antibody

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