A study from the University of British Columbia, published in Science on January 20, 2022, reported the world's first molecular-level structural analysis of the Omicron spike protein using cryo-electron microscopy (cryo-EM) at near-atomic resolution. The study revealed how this heavily mutated variant attaches to and infects human cells.

Dr. Sriram Subramaniam, Professor of Biochemistry and Molecular Biology at UBC and corresponding author, stated: "Understanding the molecular structure of the viral spike protein is critical because it will enable us to develop more effective treatments against Omicron and related variants. By analyzing how this virus infects human cells, we can develop better therapies to disrupt this process and neutralize the virus."

Omicron carries 37 mutations on its spike protein—3 to 5 times more than previous variants.

Structural analysis revealed that multiple mutations (R493, S496, R498) create new salt bridges and hydrogen bonds between the spike protein and the ACE2 receptor, increasing binding affinity, while other mutations (K417N) reduce binding strength.

Dr. Subramaniam concluded: "Overall, these findings show that Omicron has greater binding affinity than the original SARS-CoV-2, at levels similar to Delta. It is remarkable that Omicron maintains its ability to bind human cells despite such extensive mutations."

The study also showed that Omicron spike protein exhibits enhanced antibody evasion—measurable evasion against all six tested monoclonal antibodies, with complete evasion of five. The variant also showed enhanced evasion of antibodies from vaccinated and unvaccinated COVID-19 patients. Notably, Omicron evaded vaccine-induced immunity less effectively than natural immunity from unvaccinated patients, reinforcing vaccination as the best defense.

The researchers concluded that the combination of increased binding affinity and antibody evasion likely contributes to Omicron's enhanced transmissibility. The research team will continue to focus on understanding neutralizing antibody combinations effective against all SARS-CoV-2 variants.