The weakness can be targeted by neutralising antibodies, paving the way for universally effective treatments
Scientists have found a key vulnerability across all major variants of the SARS-CoV-2 virus, including the recently emerged BA.1 and BA.2 Omicron subvariants.
Drug manufacturers can now exploit this weakness in the protein structure of the virus. The spot is relatively mutation-free, so the resulting treatments could be effective against existing — and even future — variants.
The findings were published in the journal Nature Communications August 29, 2022.
SARS-CoV-2 is a highly adaptable virus that has evolved to evade most existing antibody treatments, said the study’s senior author Sriram Subramaniam. “The virus can evade much of the immunity conferred by vaccines and natural infection,” said Subramaniam, a professor at UBC’s faculty of medicine.
Read more: AI helps scientists keep up in COVID-19 mutation race
The researchers used cryo-electron microscopy to reveal the atomic-level structure of the virus’ spike protein. They found the vulnerable spot, known as an epitope. An antibody fragment called VH Ab6 is able to attach to this site and neutralise each major variant, they found.
Subramaniam said:
This study reveals a weak spot that is largely unchanged across variants and can be neutralised by an antibody fragment. It sets the stage for the design of pan-variant treatments that could potentially help a lot of vulnerable people.
Our bodies naturally produce antibodies to fight infection, but they can also be made in a laboratory and administered to patients as a treatment. While several antibody treatments have been developed for COVID-19, their effectiveness has waned in the face of highly-mutated variants like Omicron.
“Antibodies attach to a virus in a precise manner, like a key going into a lock. But when the virus mutates, the key no longer fits,” said Subramaniam. “We’ve been looking for master keys — antibodies that continue to neutralise the virus even after extensive mutations.”
We now have a clear picture of this vulnerable spot on the virus, the study author said. “We know every interaction the spike protein makes with the antibody at this site. We can work backwards from this, using intelligent design, to develop a slew of antibody treatments,” he said.
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Cryo-electron microscopy reveals how the VH Ab6 antibody fragment (red) attaches to the vulnerable site on the SARS-CoV-2 spike protein (grey) to block the virus from binding with the human ACE2 cell receptor (blue). Photo: Sriram Subramaniam / UBC.png)
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