By Doug Bennett
GAINESVILLE — A University of Florida Health researcher has successfully analyzed the many mutations in the omicron variant of the SARS-CoV-2 virus, a crucial step in better understanding the variant’s potential threat and ways to combat it.
Immunologist David A. Ostrov, Ph.D., was asked by a worldwide consortium of scientists to analyze and map the locations of omicron’s mutations. His analysis for the Global Virus Network found omicron has substantially more mutations than the delta variant at four key sites within the virus. At least one of those sites — which may affect omicron’s transmissibility — has more than three times as many mutations as the delta variant, Ostrov found.
Mapping omicron’s mutations helps scientists around the world better understand its potential for immune system evasion, transmissibility and mortality.
Early reports from around the world linked omicron with mild disease but experts say more data are needed. Scientists elsewhere have said omicron is about five times more transmissible than delta — a point that was backed up by Ostrov’s analysis.
“The mutations strongly suggest very high transmissibility. And there are a number of mutations that are completely unknown in terms of their function,” said Ostrov, an associate professor in the UF College of Medicine’s department of pathology, immunology and laboratory medicine.
Ostrov said it’s not just the number of mutations that are concerning but more importantly their locations. The virus appears to be mutating in unexpected places, which Ostrov said suggests it is trying to evade a protein known as a co-receptor. Sometimes, co-receptors can stop viruses from infecting a cell.
A group of seven “interchain” mutations is also accelerating a process that leads to infection, Ostrov said. The mutations allow the virus to attach to a host cell and “drag” the virus membrane inside.
In another key part of omicron, Ostrov found 14 mutations compared with just two in the delta variant. Those mutations, located in an area known as the receptor-binding domain, allow the virus to dock to receptors and enter cells, leading to infection.
Omicron is currently classified as a variant of concern by the Centers for Disease Control and Prevention, meaning there is evidence of increased transmissibility or other factors such as diminished vaccine or antibody effectiveness. If it shows an ability to evade diagnostic tests, diminish vaccine effectiveness or cause more severe disease, omicron would be elevated to a variant of high consequence.
“As a variant of concern, it looks like omicron also has the potential to be a variant of high consequence,” Ostrov said.
While the analysis of omicron mutations is concerning, Ostrov said it’s also a starting point for strategizing ways to contain and neutralize the variant. Discussions are underway about starting a human clinical trial in South Africa, where omicron was first detected. It would study the effectiveness of two common compounds found to inhibit the SARS-CoV-2 virus. Late last month, Ostrov and his colleagues published results showing a combination of an over-the-counter antihistamine and a protein found in cow’s milk reduce virus replication by 99% in human and monkey cells.
“A clinical trial takes time, but we already know that a combination of safe, approved drugs can inhibit replication of the coronavirus,” he said.
The omicron analysis comes shortly after Ostrov and UF colleague discovered a previously unrecognized pattern of mutations in the coronavirus. That pattern of mutations apparently has strong effects on the transmissibility of SARS-CoV-2. Mutations in these patterns should be looked at carefully and be used as the basis for artificial intelligence prediction of emerging variants, Ostrov said. The findings could be used to develop new antiviral drugs and vaccines against variants likely to emerge, according to Ostrov and Glenn W. Knox, M.D., an associate professor of surgery at the UF College of Medicine – Jacksonville.
More broadly, Ostrov said antiviral drug combinations hold significant promise against the coronavirus — similar to how antivirals were deployed against HIV and hepatitis C.
“We need to use every tool in the toolbox to inhibit the replication of this virus,” Ostrov said. “We should be vaccinating. We should be giving booster shots. We should be updating the vaccines with the sequences of currently circulating viruses. And we should be considering combinations of antiviral drugs.”