Researchers from the University of British Columbia (UBC) have become the first in the world to conduct a molecular-level structural analysis of the Omicron spike protein, which helps the virus enter and infected cells. The researchers, including Indian-origin scientists Dr Sriram Subramaniam, believe that the latest analysis could help accelerate the development of more effective treatments against the COVID-19 variant.
“UBC researchers are the first in the world to conduct a molecular-level structural analysis of the Omicron variant spike protein”, the University said in a statement.
The findings published in the Science Journal shed new light on why Omicron is highly transmissible, and it will also help accelerate the development of more effective treatments, according to a statement issued by UBC. Subramaniam, who is a professor in the UBC faculty of medicine’s department of biochemistry and molecular biology, explained that the Omicron has greater binding affinity than the original SARS-CoV-2 virus, with levels more comparable to what seen with the Delta strain.
Subramaniam said that the analysis reveals how the heavily mutated variant infects human cells and is highly evasive of immunity. He also went on to discuss the implications of his team’s research and underlined that “vaccination remains our best defence against Omicron strain”. The UBC professor added that the findings also show string antibody evasion and binding with human cells that contribute to increased transmissibility.
Subramaniam said, “the Omicron variant is unprecedented for having 37 spike protein mutations, that’s three to five times more mutations than any other variant we’ve seen”.
The professor explained that this is important for two reasons. Firstly, the spike protein is how the virus attacks and infects human cells. Secondly, Subramaniam said that it is because antibodies attach to the spike protein in order to neutralise the virus. Therefore, he added that small mutations on the spike protein have potentially big implications for how the virus is transmitted, how our body fights it off, and the effectiveness of treatments.
“Our study used cryo-electron microscopy and other tests to understand how mutations impact the behaviour of the Omicron variant at a molecular level”, Subramaniam said.
Omicron spike protein far better at evading monoclonal antibodies
Further, Dr Sriram Subramaniam explained that several mutations create new salt bridges and hydrogen bonds between the spike protein and the human cell receptor known as ACE2. The professor said that this appears to increase binding affinity, how strongly the virus attaches to human cells, while other mutations (K417N) decrease the strength of this bond. He added that it is remarkable that the Omicron strain evolved to retain its ability to bind with human cells efficiently despite such extensive mutations.
“Our experiments confirm what we’re seeing in the real world, that the Omicron spike protein is far better than other variants at evading monoclonal antibodies that are commonly used as treatments, as well as at evading the immunity produced by both vaccines and natural infection”, he said.
Moreover, according to the research, both the characteristic seen as a result of spike protein mutations, strong binding with human cells, and increased antibody evasion, are likely contributing factors to the increased transmissibility of the Omicron strain. The aforementioned characteristics are the underlying mechanisms fuelling the variant’s rapid spread and why Omicron could become the dominant variant of SARS-CoV-2 very quickly, the study 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 that process and neutralise the virus”, Subramaniam added.