Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry
| Autor: | Lin Cheng, Qiang Ding, Jiwan Ge, Bing Zhou, Zheng Zhang, Lei Liu, Yuling Tian, Jing Sun, Peng Chen, Juanjuan Zhao, Xuanling Shi, Qi Zhang, Xinquan Wang, Shuo Song, Sisi Shan, Jincun Zhao, Senyan Zhang, Ruoke Wang, Linqi Zhang, Bin Ju, Haiyan Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular 0301 basic medicine Protein Conformation viruses General Physics and Astronomy Plasma protein binding Antibodies Viral Neutralization Epitope Epitopes Mice 0302 clinical medicine Receptor chemistry.chemical_classification Mice Inbred BALB C Multidisciplinary biology Chemistry Antibodies Monoclonal Spike Glycoprotein Coronavirus Receptors Virus Angiotensin-Converting Enzyme 2 Antibody Infection Protein Binding medicine.drug_class Science Monoclonal antibody Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine Animals Humans Binding site Binding Sites SARS-CoV-2 COVID-19 General Chemistry Virus Internalization biochemical phenomena metabolism and nutrition Antibodies Neutralizing Virology COVID-19 Drug Treatment Disease Models Animal HEK293 Cells 030104 developmental biology biology.protein Glycoprotein 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-9 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Understanding the mechanism for antibody neutralization of SARS-CoV-2 is critical for the development of effective therapeutics and vaccines. We recently isolated a large number of monoclonal antibodies from SARS-CoV-2 infected individuals. Here we select the top three most potent yet variable neutralizing antibodies for in-depth structural and functional analyses. Crystal structural comparisons reveal differences in the angles of approach to the receptor binding domain (RBD), the size of the buried surface areas, and the key binding residues on the RBD of the viral spike glycoprotein. One antibody, P2C-1F11, most closely mimics binding of receptor ACE2, displays the most potent neutralizing activity in vitro and conferred strong protection against SARS-CoV-2 infection in Ad5-hACE2-sensitized mice. It also occupies the largest binding surface and demonstrates the highest binding affinity to RBD. More interestingly, P2C-1F11 triggers rapid and extensive shedding of S1 from the cell-surface expressed spike glycoprotein, with only minimal such effect by the remaining two antibodies. These results offer a structural and functional basis for potent neutralization via disruption of the very first and critical steps for SARS-CoV-2 cell entry. Here, the authors compare the crystal structures and investigate the neutralization mechanisms of three neutralizing antibodies against SARS-CoV-2 and find that one antibody, P2C-1F11, closely mimics binding of receptor ACE2 and displays the most potent neutralizing activity in vitro, as well as conferring protection against SARS-CoV-2 infection in Ad5-hACE2-sensitized mice. |
| Databáze: | OpenAIRE |
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