Omicron Spike Protein More Mutated than Previous Variants

The world’s first molecular-level structural analysis of the Omicron variant’s spike protein may explain why the mutated virus is more transmissible than previous variants and is better able to evade antibody defenses in vaccinated individuals and those previously infected with COVID-19.

Using cryo-electron microscopy, researchers at the University of British Columbia’s (UBC) faculty of medicine were able to identify 37 mutations on Omicron’s spike variant—three to five times more than previous variants. Several mutations appear to increase how strongly the virus attaches to cells by creating new salt bridges and hydrogen bonds between the spike protein and the human cell receptor ACE2. One other mutation, however, appeared to lessen the bond.

“Overall, the findings show that Omicron has greater binding affinity than the original virus, with levels more comparable to what we see with the Delta variant,” says Dr. Sriram Subramaniam, professor in UBC’s department of biochemistry and molecular biology and lead author of the study.  “It is remarkable that the Omicron variant evolved to retain its ability to bind with human cells despite such extensive mutations.”

The researchers also found that Omicron’s spike protein exhibited increased antibody evasion compared to previous variants. They found measurable evasion from all six monoclonal antibodies tested, and complete escape from five.

“Notably, Omicron was less evasive of the immunity created by vaccines, compared to immunity from natural infection in unvaccinated patients. This suggests that vaccination remains our best defense,” says Subramaniam.

Next, Subramaniam says his research team will work to  better understand the binding of neutralizing antibodies and how that can be used to develop variant-resistant treatments.

“Understanding the molecular structure of the viral spike protein is important as it will allow us to develop more effective treatments against Omicron and related variants in the future,” Subramaniam  says. “By analyzing the mechanisms by which the virus infects human cells, we can develop better treatments that disrupt that process and neutralize the virus.”

The paper, entitled “SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex,” was published recently last week in Science.