Indian-origin scientists among UBC researchers present the world’s first molecular-level analysis of omicron – Archyde

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

A team of researchers, including a scientist of Indian descent from the prestigious University of British Columbia, has become the world’s first to perform a molecular-level structural analysis of the omicron spike protein, which could help accelerate the development of more effective treatments against the variant.

Spike protein helps the virus enter and infect cells.

dr Sriram Subramaniam, a professor in the Department of Biochemistry and Molecular Biology at UBC School of Medicine, said that Omicron has greater binding affinity than the original SARS-CoV-2 virus, with levels more comparable to those of the Delta variant.

The findings, published in Science Journal, 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, shows how the severely mutated variant infects human cells and severely evades immunity from the Omicron variant.”

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

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

dr Subramaniam said, “The Omicron variant is unprecedented because it has 37 spike protein mutations, three to five times more mutations than any other variant we’ve seen.”

This is important for two reasons. First, because the virus attaches to and infects human cells through the spike protein. Second, because antibodies bind to the spike protein 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, 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, how tightly the virus binds to human cells, while other mutations (K417N) decrease the strength of that binding, Dr. Subramaniam.

He said it’s remarkable that the omicron variant has evolved to retain its ability to bind efficiently to human cells despite such extensive mutations.

“Our experiments confirm what we are seeing in the real world, that the Omicron spike protein is much better than other variants at evading monoclonal antibodies commonly used as treatments, as well as evading immunity, which is both provided by vaccines as well as being generated by natural infections,” he said.

In particular, Omicron was less evasive of vaccine-generated immunity than immunity that results from natural infection in unvaccinated COVID-19 patients, he said.

Both traits seen as a result of spike protein mutations, strong binding to human cells and increased antibody evasion, likely contribute to the increased transmissibility of the omicron variant, he said.

These are the underlying mechanisms that fuel the variant’s rapid spread 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. If we understand how the virus attaches to and infects human cells, we can develop treatments that disrupt this process and neutralize the virus.

“A key area of ​​focus for our team is to better understand the binding of neutralizing antibodies and treatments that are effective across the variant spectrum and how these can be used to develop variant-resistant treatments,” added Subramaniam.

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

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