A structural model of how the Omicron variant attaches to cells and antibodies sheds light on its behavior and will help in designing neutralizing antibodies, according to researchers.
Using computer models of the spike protein on Omicron’s surface, they analyzed molecular interactions occurring when the spike grabs onto a cell-surface protein called ACE2, the virus’s gateway into the cell.
Metaphorically, the original virus had a handshake with ACE2, but Omicron’s grip “looks more like a couple holding hands with their fingers entwined,” said Joseph Lubin of Rutgers University in New Jersey. The “molecular anatomy” of the grip may assist in explaining how Omicron’s mutations cooperate to help it infect cells, Lubin added.
The research team also modeled the spike with different classes of antibodies trying to attack it. The antibodies attack from different angles, “like a football team’s defense might tackle a ball carrier,” with one person grabbing from behind, another from the front, Lubin said. Some antibodies “appear likely to get shaken off” while others are likely to remain effective. Booster vaccines raise antibody levels, resulting in “more defenders,” which might compensate to some extent for “a weaker grip of an individual antibody,” Lubin said.
The findings, posted on Monday on the website bioRxiv ahead of peer review, need to be verified, “particularly with real-world samples from people,” Lubin said. “While our molecular structure predictions are by no means a final word on Omicron, (we hope) they enable a faster and more effective response from the global community.”
