Structure and function analysis of a potent human neutralizing antibody CA521FALA against SARS-CoV-2.

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, CA521FALA, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521FALA showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521FALA also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521FALA 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 CA521FALA recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521FALA 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 CA521FALA a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.

• Authors: Deyong 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
• Journal: Communications biology (Commun Biol) Vol. 4 Issue 1 Pg. 500 (04 23 2021) ISSN: 2399-3642 [Electronic] England
• PMID: 33893388 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Receptors, Virus
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2 (immunology, metabolism)
• Animals
• Antibodies, Monoclonal (immunology, pharmacology)
• Antibodies, Neutralizing (immunology, pharmacology)
• COVID-19 (epidemiology, prevention & control, virology)
• Humans
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Pandemics
• Protein Binding (drug effects)
• Receptors, Virus (immunology, metabolism)
• SARS-CoV-2 (immunology, metabolism, physiology)
• Spike Glycoprotein, Coronavirus (immunology, metabolism)
• Mice