Scientists discover ‘weak spot’ across major SARS-CoV-2 variants

Researchers, led by an Indo-Canadian scientist, say they have discovered a common vulnerability across major variants of Covid-19 SARS-CoV-2, including the more transmissible Omicron subvariants, according to a study published on Thursday, offering the possibility of a targeted antibody treatment.

The study was conducted by collaboration between researchers at Canada’s University of British Columbia - led by Dr Sriram Subramaniam, a professor at the faculty of medicine - and the University of Pittsburgh, US - led by Drs. Mitko Dimitrov and Wei Li. It was published as a peer-reviewed article in the journal Nature Communications.

The study 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. This powerful imaging technology uses beams of electrons to visualise the shapes of tissues and cells using ultra-cooling (“cryo”) techniques. Since the Covid-19 virus is 100,000 times smaller than the size of a pinhead, it is undetectable using a regular light microscope.

Antibodies attach to a virus in a specific manner, “like a key going into a lock”, according to Subramaniam, who did his MSc in Chemistry from IIT-Kanpur. However, when the virus mutates, the key no longer fits.

“We’ve been looking for master keys — antibodies that continue to neutralize the virus even after extensive mutations,” he added.

“The ‘master key’ identified in this new paper 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 neutralizes SARS-CoV-2 by attaching to the epitope on the spike protein and blocking the virus from entering human cells,” a statement from University of British Columbia explained.

“This study reveals a weak spot that is largely unchanged across variants and can be neutralized 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, who is also the study’s senior author, said.

He said this key vulnerability can now be exploited by drug manufacturers, and as the site is relatively mutation-free, the resulting treatments could be effective against existing—and even future—variants.

“We now have a very clear picture of this vulnerable spot on the virus. 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.

“Now that we’ve described the structure of this site in detail, it unlocks a whole new realm of treatment possibilities,” he said.