Indian-born scientist among UBC researchers unveils world’s first molecular-level analysis of Omicron

A team of researchers, including an Indian-born scientist from the prestigious University of British Columbia, has become the first in the world to perform molecular-level structural analysis of the breakthrough protein Omicron, which could help speed up the development of more effective treatments. against the variant.

The spike protein helps the virus enter and infect cells.

Dr. Sriram Subramaniam, a professor in the department of biochemistry and molecular biology at UBC’s medical school, said Omicron has a higher binding affinity than the original SARS-CoV-2 virus, with levels more comparable to those observed with the Delta variant.

The findings, published in the journal Science, shed new light on why Omicron is highly transmissible and will help accelerate the development of more effective treatments, according to a statement from the Vancouver-based university.

The analysis, performed at near-atomic resolution using a cryo-electron microscope, reveals how the highly mutated variant infects human cells and is highly evasive of immunity,

Subramaniam discussed the implications of his team’s research and stressed that “vaccination remains our best defense against the Omicron variant.”

The results show strong antibody evasion and binding with human cells that contribute to increased transmissibility, and that vaccination remains the best defense, the university said.

“UBC researchers are the first in the world to perform molecular-level structural analysis of the variant spike protein Omicron,” he said.

Subramaniam said “the Omicron variant is unprecedented for having 37 peak protein mutations, that’s three to five times more mutations than any other variant we’ve seen”.

This is important for two reasons. First, because the spike protein is how the virus attaches to and infects human cells. Second, because the antibodies attach to the spike protein in order to neutralize the virus, he said.

“Therefore, small mutations on the spike protein have potentially large implications for how the virus is transmitted, how our bodies fight it off, and the effectiveness of treatments.

“Our study used cryo-electron microscopy and other tests to understand how mutations affect the behavior of the Omicron variant at the molecular level,” Subramaniam said.

He said several mutations (R493, S496 and R498) create new salt bridges and hydrogen bonds between the spike protein and the human cell receptor known as ACE2.

This appears to increase binding affinity, the strength with which the virus attaches to human cells, while other mutations (K417N) decrease the strength of this binding, Subramaniam said.

He said it was remarkable that the Omicron variant had evolved to retain its ability to bind effectively to human cells despite such large mutations.

“Our experiments confirm what we see in the real world, which is that the Omicron spike protein is much better than other variants at evading monoclonal antibodies commonly used as treatments, as well as evading immunity produced both through vaccines and natural infection,” he said.

Notably, Omicron was less elusive of vaccine-created immunity, compared to immunity resulting from natural infection in unvaccinated COVID-19 patients, he said.

The two characteristics observed following spike protein mutations, strong binding to human cells and increased antibody evasion, are likely factors contributing to the increased transmissibility of the Omicron variant, a he declared.

These are the underlying mechanisms that are fueling the rapid spread of the variant and why Omicron could very quickly become the dominant variant of SARS-CoV-2, he said.

“The good news is that knowing the molecular structure of the spike protein will allow us to develop more effective treatments against Omicron and related variants in the future. Understanding how the virus attaches to and infects human cells means we can develop treatments that disrupt this process and neutralize the virus.

“An important goal for our team is to better understand the binding of neutralizing antibodies and treatments that will be effective across the range of variants, and how these can be used to develop variant-resistant treatments,” Subramaniam added.

Omicron was first identified in South Africa and Botswana in November and is behind the current wave of infections.

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