Researchers at the University of British Columbia have discovered a “weak spot” in all the major variants of the virus that causes COVID-19, a breakthrough that could lead to universally effective treatments.
In a study published Thursday in nature communicationsthe researchers used a process called cryo-electron microscopy.
This new technology allows researchers to quickly freeze proteins at the atomic level so they can take hundreds of thousands of X-ray-like snapshots of individual proteins.
“Then we can computationally combine them in 3D to create the atomic landscape of what the protein looks like,” said Dr. Sriram Subramaniam, a professor in the UBC School of Medicine and lead author of the study.
“So, in this particular case, what we’re reporting is one of many examples where we’re using the technology to literally be observers at the site of contact between an antibody and the spike protein.”
And what they found was an antibody fragment that can bind to this site and neutralize each major variant.
”It is very powerful and allows us to observe in atomic detail what the interactions are. And of course that lays the groundwork for developing therapies in the future.”
Subramaniam said SARS-CoV-2 is a highly adaptable virus that has evolved to evade most existing antibody treatments, and what its study does is reveal a weak spot that remains largely unchanged in the variants that can be neutralized by an antibody fragment.
“This is a highly adaptable virus that has evolved to evade most existing antibody treatments, as well as much of the immunity conferred by vaccines and natural infection,” he said, adding that finding a The vulnerability site that didn’t change that much in all these variants was interesting.
“Antibodies attach to a virus in a very specific way, like a key fitting into a lock. But when the virus mutates, the key no longer fits… We have been looking for master keys.”
The “master key” identified in this new paper is the VH Ab6 antibody fragment, which was shown to be effective against Alpha, Beta, Gamma, Delta, Kappa, Epsilon, and Omicron variants. The fragment neutralizes SARS-CoV-2 by binding to the epitope on the spike protein and blocking the virus from entering human cells.
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Subramaniam said it’s too early to say whether this will lead to a single vaccine for all mutations, but what they have discovered is the ability to focus and tell which part of the virus is important. This can be used by pharmaceutical companies to find a treatment.
“And this is where we focused our efforts because, look, he survived. It survived major mutations throughout the entire pandemic… So I think it gives us lesson zero, and essentially it’s finding this hotspot to zero in on our efforts to get the best antibodies that do the job of blocking viral entry.
The discovery is a collaboration between Subramaniam’s team at UBC and colleagues at the University of Pittsburgh, led by Drs. Mitko Dimitrov and Wei Li.
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