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The receptor binding domain (RBD) of the new coronavirus spike glycoprotein is a key site that mediates the binding of the virus to the host cell ACE2 receptor, and is also a key target for neutralizing antibodies and vaccines
.
Effective monitoring of key antigen changes in RBD and early response to immune escape caused by it are of important scientific significance
.
Although epidemiological research around the world has produced a large number of viral genome sequences and quickly shared them through the GISAID project, these data are essential for monitoring the spread of the virus and understanding its evolutionary mechanism
.
However, there are still many challenges in how to effectively track the immune escape and antigen change laws of mutant strains of the new coronavirus from the massive epidemiological data
.
The molecular mechanism of the introduction of mutations that may cause the drift of RBD antigen and the key amino acids that cause the failure of the antibody function are still not very clear
.
As a result, effective early warning cannot be given before the rapid spread of new variants of the new coronavirus
.
Recently, Sun Bing’s research group from the Center for Excellence in Molecular Cell Science (Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences collaborated with Lu Hongzhou’s team at the then Shanghai Public Health Clinical Center (affiliated to Fudan University) and Xie Youhua’s team at Fudan University School of Basic Medicine.
Published a research paper titled: Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants in Genome Medicine
.
The study systematically revealed the main classification of neutralizing antibody epitopes induced by the receptor binding domain (RBD) of the new coronavirus (SARS-CoV-2)
.
And in-depth analysis of the changes in the escape neutralizing antibody of the new coronavirus mutant and the potential key amino acid sites, which provide key scientific basis and information for monitoring the effectiveness of the new coronavirus mutant and predictive vaccines, monoclonal antibodies, and serological diagnosis.
Test methods that can be used for reference
.
Based on previous work, the research team isolated 93 RBD-specific antibodies from people who have recovered from the new coronavirus infection and combined with the reported antibodies.
Using alanine scanning and epitope competition experiments, the protective epitopes on RBD were systematically Divided into four categories
.
The study found that most of the neutralizing antibodies mainly recognize the first and second epitopes; and the neutralizing antibodies that can cross-bind SARS-CoV-2 and SARS-CoV mainly recognize the third and fourth epitopes.
This type of epitope is mainly located in the RBD core region and significantly affects the stability of RBD.
It has a certain degree of conservation in evolution, and cross-antibodies targeting this position can limit the escape of virus immunity
.
a.
Neutralizing activity of 93 RBD-specific antibodies from 4 COVID-19 rehabilitation patients, b.
Using monoclonal antibody discs to divide epitopes into four major categories, c.
The structure-activity relationship between epitopes and neutralizing activity, d.
The structure-activity relationship between the epitope and the ability to cross-recognize SARS-CoV and SARS-CoV-2, e.
The neutralizing ability of monoclonal neutralizing antibodies against natural mutant strains, f.
The peripheral serum of patients with new crown rehabilitation against natural mutations The neutralizing ability of the strain
.
With the help of the new crown data sharing platform, researchers targeted the antibody binding hot spots on each RBD antigen site to monitor the impact of single-point mutants and multi-point mutants on antibody escape, and identified multiple unreported causes The key natural mutation sites of RBD where the activity of neutralizing antibody is weakened or disappeared
.
Multi-point mutations (such as the Beta strain) can significantly reduce the neutralizing activity of most monoclonal antibodies and the peripheral plasma of recovered patients
.
The focus of future work is to be alert to the serious harm caused by multiple mutations of different epitopes
.
Yi Chunyan and Sun Xiaoyu, postdoctoral fellows of the Sun Bing Research Group of the Center of Molecular Cellular Excellence, Dr.
Lin Yixiao from the Lu Hongzhou team of the Public Health Clinical Center of Shanghai (Affiliated to Fudan University), and Gu Chenjian, a postdoctoral fellow from the Xie Youhua team of School of Basic Medicine, Fudan University One author
.
Researcher Sun Bing, Professor Lu Hongzhou, Professor Xie Youhua and Associate Researcher Ling Zhiyang are the co-corresponding authors of this article
.
Link to the paper: https://doi.
org/10.
1186/s13073-021-00985-w Open for reprinting, welcome to forward to Moments and WeChat groups
.
Effective monitoring of key antigen changes in RBD and early response to immune escape caused by it are of important scientific significance
.
Although epidemiological research around the world has produced a large number of viral genome sequences and quickly shared them through the GISAID project, these data are essential for monitoring the spread of the virus and understanding its evolutionary mechanism
.
However, there are still many challenges in how to effectively track the immune escape and antigen change laws of mutant strains of the new coronavirus from the massive epidemiological data
.
The molecular mechanism of the introduction of mutations that may cause the drift of RBD antigen and the key amino acids that cause the failure of the antibody function are still not very clear
.
As a result, effective early warning cannot be given before the rapid spread of new variants of the new coronavirus
.
Recently, Sun Bing’s research group from the Center for Excellence in Molecular Cell Science (Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences collaborated with Lu Hongzhou’s team at the then Shanghai Public Health Clinical Center (affiliated to Fudan University) and Xie Youhua’s team at Fudan University School of Basic Medicine.
Published a research paper titled: Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants in Genome Medicine
.
The study systematically revealed the main classification of neutralizing antibody epitopes induced by the receptor binding domain (RBD) of the new coronavirus (SARS-CoV-2)
.
And in-depth analysis of the changes in the escape neutralizing antibody of the new coronavirus mutant and the potential key amino acid sites, which provide key scientific basis and information for monitoring the effectiveness of the new coronavirus mutant and predictive vaccines, monoclonal antibodies, and serological diagnosis.
Test methods that can be used for reference
.
Based on previous work, the research team isolated 93 RBD-specific antibodies from people who have recovered from the new coronavirus infection and combined with the reported antibodies.
Using alanine scanning and epitope competition experiments, the protective epitopes on RBD were systematically Divided into four categories
.
The study found that most of the neutralizing antibodies mainly recognize the first and second epitopes; and the neutralizing antibodies that can cross-bind SARS-CoV-2 and SARS-CoV mainly recognize the third and fourth epitopes.
This type of epitope is mainly located in the RBD core region and significantly affects the stability of RBD.
It has a certain degree of conservation in evolution, and cross-antibodies targeting this position can limit the escape of virus immunity
.
a.
Neutralizing activity of 93 RBD-specific antibodies from 4 COVID-19 rehabilitation patients, b.
Using monoclonal antibody discs to divide epitopes into four major categories, c.
The structure-activity relationship between epitopes and neutralizing activity, d.
The structure-activity relationship between the epitope and the ability to cross-recognize SARS-CoV and SARS-CoV-2, e.
The neutralizing ability of monoclonal neutralizing antibodies against natural mutant strains, f.
The peripheral serum of patients with new crown rehabilitation against natural mutations The neutralizing ability of the strain
.
With the help of the new crown data sharing platform, researchers targeted the antibody binding hot spots on each RBD antigen site to monitor the impact of single-point mutants and multi-point mutants on antibody escape, and identified multiple unreported causes The key natural mutation sites of RBD where the activity of neutralizing antibody is weakened or disappeared
.
Multi-point mutations (such as the Beta strain) can significantly reduce the neutralizing activity of most monoclonal antibodies and the peripheral plasma of recovered patients
.
The focus of future work is to be alert to the serious harm caused by multiple mutations of different epitopes
.
Yi Chunyan and Sun Xiaoyu, postdoctoral fellows of the Sun Bing Research Group of the Center of Molecular Cellular Excellence, Dr.
Lin Yixiao from the Lu Hongzhou team of the Public Health Clinical Center of Shanghai (Affiliated to Fudan University), and Gu Chenjian, a postdoctoral fellow from the Xie Youhua team of School of Basic Medicine, Fudan University One author
.
Researcher Sun Bing, Professor Lu Hongzhou, Professor Xie Youhua and Associate Researcher Ling Zhiyang are the co-corresponding authors of this article
.
Link to the paper: https://doi.
org/10.
1186/s13073-021-00985-w Open for reprinting, welcome to forward to Moments and WeChat groups
