Researchers find 'weak point' in major variants of COVID-19:

Researchers at the University of British Columbia have discovered a key vulnerability in all major variants of the SARS-CoV-2 virus, including subvariants BA.1 and BA.2 Omicron recently appeared.

Weakness can be targeted by neutralizing antibodies, potentially paving the way for treatments that would universally effective for all variants.

The results, published today in Mother Nature Communications, use cryo-electron microscopy (cryo-EM) to reveal the framework at the atomic level of the vulnerable spot on the virus’ spike protein, known as the epitope. The article further describes an antibody fragment called VH Ab6 which is able to bind to this site and neutralize 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 infections,” says Dr. Sriram Subramaniam (he/him) , a professor at UBC’s medical school. and the lead author of the study. “This study reveals a weak position that is largely unchanged across variants and can be neutralized by an antibody fragment. It paves the way for the design of pan-variant treatments that could potentially help many vulnerable people.”

Antibodies are produced naturally by our bodies to fight infections, but can also be made in the laboratory and given to patients as a treatment. While several antibody treatments have been developed for COVID-, their effectiveness has declined in the face of highly mutated variants like Omicron.

“Antibodies attach to a virus in a very specific way, like a key going into a lock. But when the virus mutates, the key no longer fits,” says Dr Subramaniam. “We were looking for master keys – antibodies that continue to neutralize the virus even after significant mutations.”

The “master key” identified in this new paper is the fragment of VH Ab6 antibody, which has been shown to be effective against 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 preventing the virus from entering human cells.

The discovery is the latest in a long and effective collaboration between Dr. Subramaniam’s team at UBC and his colleagues at the University of Pittsburgh, led by Drs. Mitko Dimitrov and Wei Li. The Pittsburgh team screened large libraries of antibodies and tested their effectiveness against COVID-, while the L ‘UBC used cryo-EM to study the molecular composition and characteristics of the spike protein.

Zoom in on the faint details of COVID-19

The UBC team is recognized worldwide for its experience in the use of cryo-EM to visualize protein-protein and protein-antibody interactions at atomic resolution. In another paper published earlier this year in Science, they were the first to report the structure of the hold-up zone between Omicron’s spike protein and the human cellular receptor ACE2, providing a molecular explanation for Omicron’s enhanced viral fitness.

By mapping the molecular makeup of each spike protein, the team looked for areas of vulnerability that could shed light on new treatments.

“The epitope we describe in this posting is mostly removed from hotspot mutations, which is why its abilities are preserved across variants,” says Dr. Subramaniam. “Now that we have described the composition of this web-site in detail, it opens up a whole new realm of treatment possibilities.”

Dr. Subramaniam claims that this key vulnerability may now be exploited by drugmakers, and because the web page 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 issue on the virus. We know every conversation that spike protein makes with antibody on this website. We can work backwards from this, using smart design, to develop a host of antibody treatments,” says Dr. Subramaniam. “Having broadly effective, variant-resistant treatments would be a game-changer in the ongoing fight against COVID-19.”

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