It’s one of The perplexing mystery of the Covid pandemic. Where was Omicron almost one year ago, and how did it emerge? It was extremely contagious and fast, with bizarre mutations. When scientists untangled the array, they found that Omicron wasn’t related to Delta or Alpha, the two waves that preceded it. Instead, its divergence from its closest common ancestor dated back more than a year, to the first few months of the pandemic—practically a geologic era in viral-replication time.
It was quite a puzzle. This was an unsolvable problem. There was a mystery: Omicron may have been created not from previous variants of Omicron, but parallel to these earlier versions. Where did that happen?
There were many competing hypotheses. It found refuge in people with little interaction with the outside world, and who did not participate in sequence programming. The virus had been able to find a place in an immunocompromised person, allowing it to spread and evolve. Or, a third thought: It fell back into the animal world—not into the bats in which it first found a host, but into some new species that would provoke mutation in novel ways.
This possibility was known as reverse zoonosis or stabletback. In April 2020, just a few months after the virus began spreading internationally, it migrated into mink farms in the Netherlands, triggering the deaths or preventive slaughter of millions of the animals—and a few months later it traveled back into humans.
No one has been able to say with precision which of those three hypotheses accurately explains Omicron’s arrival—and with Omicron itself spinning off variants so rapidly, the discussion dropped out of researchers’ priorities. A new research study by a team from the University of Minnesota has given this debate new energy. They found that Omicron was adapted to mice and developed its mutational pattern before being passed onto humans.
“These Omicron mutations are evolutionary traces left by the virus during its transmission from one animal species to another,” senior author Fang Li, a professor of pharmacology and director of the university’s Center for Coronavirus Research, said in a statement. Li refused to give an interview.
This study was published last week by the Proceedings of the National Academy of Sciences, researchers took a structural biology approach—studying the shapes of molecules within the virus—to examine mutations in Omicron’s spike protein, which allows it to invade cells. Researchers discovered that certain mutations made it more effective in binding to ACE2 in mice’s cells, compared with the human version. By creating non-infectious pseudoviruses to express Omicron’s spike protein, they confirmed this work and observed that the virus bound with human cells engineered for the Omicron receptors. Omicron was more compatible with the mouse-specific version, they found.