A team led by an Indian-origin researcher has discovered a key vulnerability across all major variants of SARS-CoV-2, the virus that causes COVID-19, including the recently emerged BA.1 and BA.2 Omicron subvariants.
The weakness can be targeted by neutralising antibodies, potentially paving the way for treatments that would be universally effective across variants, the researchers said.
The study, published on Thursday in the journal Nature Communications, used cryo-electron microscopy (cryo-EM) to reveal the atomic-level structure of the vulnerable spot on the virus’ spike protein, known as an epitope -or part to which an antibody attaches itself.
Spike protein is used by the SARS-CoV-2 virus to enter and infect human cells. The researchers also described an antibody fragment called VH Ab6 that is able to attach to this site and neutralise each major variant.
“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,” said Sriram Subramaniam, a professor at the University of British Columbia, and the study’s senior author.
“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,” Subramaniam said. Antibodies are naturally produced by our bodies to fight infection, but 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 very specific manner, like a key going into a lock. But when the virus mutates, the key no longer fits,” said Subramaniam.
“We have been looking for master keys — antibodies that continue to neutralise the virus even after extensive mutations,” he added.
The ‘master key’ identified by researchers is the antibody fragment VH Ab6, which was shown to be effective against the Alpha, Beta, Gamma, Delta, Kappa, Epsilon and Omicron variants.
The fragment neutralises SARS-CoV-2 by attaching to the epitope on the spike protein and blocking the virus from entering human cells.
By mapping the molecular structure of each spike protein, the team has been searching for areas of vulnerability that could inform new treatments.
“The epitope we describe in this paper is mostly removed from the hot spots for mutations, which is why its capabilities are preserved across variants,” said Subramaniam.
“Now that we have described the structure of this site in detail, it unlocks a whole new realm of treatment possibilities,” he said.
Subramaniam said this key vulnerability can now be exploited by drug makers, and because the site is relatively mutation-free, the resulting treatments could be effective against existing, and even future, variants.