The inner reason for Omicron’s high contagion has now been further uncovered by scientists. A new paper published in Science published the world‘s first molecular-level analysis of the Omicron spike protein. The study, from the University of British Columbia School of Medicine, noted that Omicron has 37 mutations in the spike protein, 3-5 times more than previous new coronavirus variants.
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Further experiments also showed that the Omicron spike protein exhibited stronger antibody escape—for all six of the monoclonal antibodies tested, and five of them were completely “evaded” by it.
Corresponding author Sriram Subramaniam said:
Understanding the molecular structure of the virus’s spike protein is critical for developing more effective treatments.
Remarkably, despite so many mutations, Omicron has evolved to retain the ability to bind to human cells.
For more research details, we refer to the paper in detail.
The most mutated variant
The day after Omicron was named by the WHO, researchers at the University of British Columbia quickly downloaded the genome sequence set posted online and sent Omicron’s genetic sample to the lab.
To figure out how the Omicron variant attaches to and infects human cells, the researchers used cryo-electron microscopy to detectBinding of Omicron to the human receptor ACE2Structural analysis at near atomic resolution was performed.
Among them, the “border” between the two (the black box in the above picture) is called “receptor binding domain”（Receptor Binding Domain，RBD）。
Electron microscopy results showed that Omicron was the most mutated variant of the new crown: a total of 37 spike protein mutations, 15 of which were present in the receptor binding domain.
The well-known delta has only 7 mutations compared to the originally isolated strain, and only 2 are present in the RBD region (in the S protein).
About the spike protein:
1. It is the way the virus adsorbs and infects human cells;
2. The RBD region where the spike protein is located is also the main target of neutralizing antibodies.
Most of the mutations in Omicron in the RBD region were found through high-throughput analysis.reduceMutations in the ability to bind to the human receptor ACE2.
Nonetheless, compared to Delta, Omicron’s affinity for human cellsdid not drop, but maintained a comparable level.
How is this going?
Further observation found that Omicron exists“Compensation Mechanism”, there are another 3 mutations (R493, S496 and R498) that create new salt bridges and hydrogen bonds between Omicron and the ACE2 receptor.
These three “returned a game” after various mutations reduced the affinity level of Omicron.
The researchers said that this shows thatAlthough the new coronavirus has undergone numerous mutations along the way, the new Omicron variant retains the ability to bind to the human receptor.
Next, the researchers conducted further experiments on the effect of the Omicron mutation on antibody neutralization.
Sources of antibodies tested include:
Monoclonal antibodies
Serum obtained from 30 two-shot individuals who had not been infected with Covid-19
Serum obtained from 68 unvaccinated Covid-19 recoveries infected with Covid-19 variants such as Alpha, Gamma or Delta
Neutralization experiments were then performed using pseudoviruses containing wild-type, delta, or Omicron S proteins to compare the ability of these pseudoviruses to evade antibodies.
Experiments on the effect of Omicron mutation on the “escape” of monoclonal antibodies found that OmicronComplete neutralization against five of the six antibodies tested。
The only fully neutralized S309 antibody (yellow), although the neutralization ability did not decrease, the effect was also diminished.
The researchers explained that this result may indicate that compared with the previous new crown variant, the Omicron spike proteinUnusually high number of mutations gives it more robust antibody evasion。
For the current vaccine/immunity effect, the researchers also conducted experiments.
The results showed that, compared with the wild type, the neutralization ability of the convalescent sera to the Omicron variant was reduced to 1/6.3 on average, while the neutralization ability of the vaccinated population was reduced to 1/4.4 of the original.
Compared with the delta variant, sera from convalescent patients showed a greater reduction in neutralization capacity (1/8.2), while the vaccinated group also showed a decrease in neutralization capacity, but to a lesser extent (1/3.4).
Despite showing greater antibody evasion, such experimental results suggest that the vaccine is still more effective against Omicron than the natural infection immunity developed by unvaccinated new crown patients.
Corresponding author Subramaniam also emphasized:
This shows that vaccines are still our best defense.
To sum up briefly, at the molecular level, the study points to a number of mutations on the surface of the Omicron spike protein that are thought to help the virus evade antibodies elicited by vaccination or previous infection.
And such widespread mutations did not affect Omicron’s ability to bind to human cells. Although mutations such as K417N affected its binding efficiency to the ACE2 receptor, other novel mutations interacted to restore this binding ability.
As the authors of the paper put it:
From all these indications, Omicron seems to have been able to selectively strike a balance between the ability of antibodies to escape and the ability of human cells to bind.
The research team of this paper is from the University of British Columbia (UBC) School of Medicine, and the corresponding author is Dr. Sriram Subramaniam, a professor in the UBC Department of Biochemistry and Molecular Biology.
He is known worldwide for his leading contributions to cryo-EM. Google Scholar shows that its h-index is 66 and the total number of citations exceeds 15,000.
One More Thing
In addition, also recently, The Lancet, an authoritative medical journal, published an opinion article saying that with the rapid spread of Omicron, the global new crown pandemic is expected toMarch this yearFinish.
The author is Christopher Murray, director of the Institute for Health Metrics and Evaluation at the University of Washington. For the past two days, his team has been tasked with modeling the coronavirus outbreak for the White House.
In his article, he stated that by March 2022, a large portion of the world will be infected with the Omicron variant. At the same time, as the vaccination rate continues to increase, the global immunization level will reach an all-time high. After that, while new coronavirus variants will still emerge, the pandemic should be contained.