Four Nature, Two Cell! The research team of Gao Fu, He Dayi and other research teams revealed the potential mechanism of Omicron antibody escape

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Written by Jevin

The pathogen SARS-CoV-2 has evolved to develop resistance to antibody-mediated neutralization
.
Several recent Omicron subvariants of the pathogen SARS-CoV-2 have shown such strong antibody resistance that the vaccine's protective effect against infection has diminished, and most current monoclonal therapies have lost their efficacy, manifested by an increasing number of breakthrough infections
during the convalescent period and/or in vaccinated individuals.

In 2022, scientists made a series of breakthroughs
in the study of SARS-CoV-2.
The following six studies were reviewed
here.

 01 

On January 5, 2022, Peiyi Wang of Southern University of Science and Technology, Gao Fu and Qi Jianxun of the Institute of Microbiology, Chinese Academy of Sciences jointly published a research paper entitled "Receptor binding and complex structures of human ACE2 to spike RBD from Omicron and Delta SARS-CoV-2" online in Cell, and the research team examined several volatile organic compounds.
Includes α, β, γ, δ, and Omicron, and demonstrates that the Omicron variant RBD binds to human ACE2 (hACE2) with an affinity comparable
to that of the prototype.
The researchers then determined the crystal and cryo-electron microscopy (cryo-EM) structure of Omicron RBD complex with hACE2 and determined the role of
key residues in receptor recognition.
In addition, the research team solved the crystal structure
of the δRBD-hACE2 complex.
The results of this study provide important molecular information on Omicron and δ volatile organic compounds, which can guide
the development of novel prevention/treatment approaches against major Omicron variants.

 02

On January 21, 2022, the research team of Zhu Xuan/Chen Fuhe/Yuan Guoyong of the University of Hong Kong and the research team of the Key Laboratory of Tropical Translational Medicine of the Ministry of Education of Hainan Medical College jointly published a research paper entitled "Attenuated replication and pathogenicity of SARS-CoV-2 B.
1.
1.
529 Omicron" online in Nature.
The researchers found that the Omicron variant was impaired in human lung cells and viral replication in the lungs of infected animals, suggesting that Omicron infection in humans may cause milder lung symptoms
compared to after infection with previous variants.
However, the Calu3 cells used in this study are cancer cells derived from human lungs and may not be an accurate representation
of human lungs.
Similarly, K18-hACE2 mice may not exactly resemble the pathogenesis
of human Omicron infection.
In addition, data from mouse models suggest that the difference in viral replication and pathogenicity between Omicron and Delta is smaller than the difference
between Omicron and WT SARS-CoV-2.
Therefore, human clinical data should be used to further evaluate the pathogenicity of Omicron in humans
.
Second, studies have shown that the Omicron variant is impaired in replication due to its reduced spike cutting and its ability to
use TMPRSS2.
Research reveals key characteristics of the Omicron variant that provide critical information
for the prevention, control and treatment of the current COVID-19 pandemic.

 03 

On March 3, 2022, Columbia University's first-year team published a research paper
titled "Antibody evasion properties of SARS-CoV-2 Omicron sublineages" online in Nature.
Studies have shown that only recently authorized betilovimab adequately treats all sublines of the Omicron variant
.
As more and more variants emerge that narrow down COVID-19 treatment options, new strategies must continue to be developed to contain this evolving pathogen
.
The study showed that no authorized monoclonal antibody therapy other than the recently authorized LY-CoV1404 adequately covers all sublineages
of the Omicron variant.

 04 

On June 15, 2022, Gao Fu, Zhao Xin, Sun Yeping and Scalper of the Institute of Microbiology, Chinese Academy of Sciences, published an online report entitled "Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.
2 and" online in Cell BA.
1.
1", they found that the binding affinity of human angiotensin-converting enzyme 2 (hACE2) to the receptor-binding domains (RBDs) of the four early Omicron subvariants (BA.
1, BA.
1.
1, BA.
2, and BA.
3) follows the order
of BA.
1.
1 > BA.
2 > BA.
3 ≈ BA.
1 。 The complex structure of hACE2 with BA.
1.
1, BA.
2 and BA.
3 RBD indicates that the hACE2 binding affinity of BA.
2 is higher than BA.
1, which is related
to the absence of G496S mutation in BA.
2.
The R346K mutation in BA.
1.
1 mainly affects the interaction network in the BA.
1.
1 RBD/hACE2 interface through long-range changes, and contributes to the hACE2 affinity of BA.
1.
1 RBD being higher than that of BA.
1 RBD
.
These results reveal the structural basis
of different hACE2 binding modes in BA.
1.
1, BA.
2 and BA.
3 RBD.

 05 

On July 5, 2022, Columbia University's team published a research paper titled "Antibody evasion by SARS-CoV-2 Omicron subvariants BA.
2.
12.
1, BA.
4, & BA.
5" online in Nature, which reported the results of systematic antigen analysis of
these surging Omicron subvariants 。 Compared to BA.
2, BA.
2.
12.
1 is only slightly more resistant (1.
8-fold)
to serum from vaccinated and booster individuals.
However, BA.
4/5 is much more resistant (4.
2-fold) and is therefore more likely to lead to vaccine breakthrough infections
.
The Omicron lineage of SARS-CoV-2 continues to evolve, producing subvariants
that are not only more transmissible but also more able to escape antibodies.

 06 

On November 9, 2022, Columbia University He collaborated with Alejandro Chavez to publish a research paper titled "Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir" online in the journal Nature, an oral antiviral drug targeting SARS-CoV-2 3CL protease.
Has been shown to be clinically effective
against COVID-19.
However, as SARS-CoV-2 develops resistance to other treatment modalities, there are concerns that the same will happen to Nirmatrelvir
.
The research team investigated this possibility
by channeling SARS-CoV-2 in vitro in nirmatrelvir using two separate methods.
The findings suggest that SARS-CoV-2 resistance to nirmatrelvir is indeed easily developed through multiple pathways in vitro, and that the specific mutations observed in this paper provide a solid basis
for studying the mechanism of resistance in detail and informing the design of next-generation protease inhibitors.

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for treatment options.
If you need health guidance, please go to a regular hospital
.