How omicron infects cells while evading immunity

In a new study published in the journal Nature Communications, researchers at the University of Minnesota identified the structural mechanism that may explain why the omicron variant is so effective in infecting people, both vaccinated and unvaccinated, and suggested ways to curb its spread.

The team of U of M scientists determined the high-resolution structure of the omicron variant’s spike protein, which functions as the virus’s key to unlock viral entry into human cells. The tip of the spike protein directly attacks human cells. It is also the virus’s vulnerable region and is the prime target of human antibody defenses.

The study found:

• The tip of the spike protein in previous viral strains is either exposed for attacking human cells or hidden from antibody defenses, a viral approach for balanced infectivity and immune evasion.
• The tip of the omicron spike protein is always exposed for attacking human cells. This may explain why omicron is so infectious.
• Compared to previous strains, the tip of the omicron spike protein has undergone extensive mutations. Thus, antibodies that target the previous strains are no longer effective against omicron. This may explain why omicron is so effective in infecting vaccinated people.

“Although omicron has evolved to become more infectious, it has also exposed its vulnerable regions that can be targeted by antibodies,” said study lead Fang Li, a professor in the College of Veterinary Medicine. “Currently, omicron is escaping immune surveillance aimed at the original viral strains, but vaccines and antibodies specifically designed to target the omicron spike protein may bring this variant under control and could potentially help us prepare for addressing future variants.”

Funding was provided by the National Institutes of Health and University of Minnesota. The study was co-led by Li and Bin Liu, an assistant professor at the Hormel Institute; and was co-authored by Gang Ye, a postdoctoral scientist in the Department of Veterinary and Biomedical Sciences. 

About the College of Veterinary Medicine
The University of Minnesota College of Veterinary Medicine affects the lives of animals and people every day through educational, research, service, and outreach programs. Established in 1947, the University of Minnesota College of Veterinary Medicine is Minnesota’s only veterinary college. Fully accredited, the college has graduated over 4,000 veterinarians and hundreds of scientists. The college is also home to the Veterinary Medical Center, the Veterinary Diagnostic Laboratory, the Leatherdale Equine Center and The Raptor Center. To learn more, visit vetmed.umn.edu.