New COVID-19 nasal spray outperforms current antibody treatments in mice
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Loading... - Spencer Hamilton
- 14 Apr 2022
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Current antibody treatments block SARS-CoV-2 by binding to one of three binding sites on the spike protein. A new protein-based antiviral binds to all three sites on the spike protein, making it more effective than current therapies. The new therapy also is low-cost, easy to manufacture, does not require complicated supply chains with extreme refrigeration and potentially could be self-administered.
A new protein-based antiviral nasal spray developed by researchers at Northwestern University, University of Washington and Washington University at St. Louis is being advanced toward Phase I human clinical trials to treat COVID-19.
Designed computationally and refined in the laboratory, the new protein therapies thwarted infection by interfering with the virus' ability to enter cells. The top protein neutralized the virus with similar or greater potency than antibody treatments with Emergency Use Authorization status from the U.S. Food and Drug Administration (FDA). Notably, the top protein also neutralized all tested SARS-CoV-2 variants, something that many clinical antibodies have failed to do.
When researchers administered the treatment to mice as a nasal spray, they found that the best of these antiviral proteins reduced symptoms of infection -- or even prevented infection outright.
The findings were published yesterday (April 12) in the journal Science Translational Medicine.
This work was led by Northwestern's Michael Jewett; David Baker and David Veesler at the University of Washington School of Medicine; and Michael S. Diamond at WashU.
To begin, the team first used supercomputers to design proteins that could stick to vulnerable sites on the surface of the novel coronavirus, targeting the spike protein. This work was originally reported in 2020 in the journal Science.
In the new work, the team reengineered the proteins -- called minibinders -- to make them even more potent. Rather than targeting just one site of the virus' infectious machinery, the minibinders simultaneously bind to three sites, making the drug less likely to detach.
"SARS-CoV-2's spike protein has three binding domains, and common antibody therapies may only block one," Jewett said. "Our minibinders sit on top of the spike protein like a tripod and block all three. The interaction between the spike protein and our antiviral is among the tightest interactions known in biology. When we put the spike protein and our antiviral therapeutic in a test tube together for a week, they stayed connected and never fell apart."
Jewett is a professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and director of Northwestern's Center for Synthetic Biology. Andrew C. Hunt, a graduate research fellow in Jewett's laboratory, is the paper's co-first author.
As the SARS-CoV-2 virus has mutated to create new variants, some treatments have become less effective in fighting the ever-evolving virus. Just last month, the FDA paused several monoclonal antibody treatments, for example, due to their failure against the BA.2 omicron subvariant. Read More…
