Antibody “master key” discovery could neutralize all COVID variants

 

A new study published in Nature Communications has homed in on a part of the SARS-CoV-2 spike protein that seems to be shared across all known variants. The research also reveals an antibody fragment that can hypothetically block the virus from entering human cells, paving the way for future therapies to neutralize all COVID-19 variants.

The new research offers one of the most thorough investigations to date into the spike protein differences between a number of SARS-CoV-2 variants. Using cryo-electron microscopy the study zoomed in on spike proteins from Alpha, Beta, Gamma, Delta, Kappa, Epsilon, and Omicron (BA.1 and BA.2) variants.

The researchers discovered a certain part of the spike protein is conserved across all these variants. This spot, known as an epitope, is vulnerable to novel antibodies that could block the virus' ability to infect human cells.

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

Antibodies work to block infection by fitting into those epitopes on the viral spike protein and interrupting the way the virus would lock onto human cells. The new research describes the development of an antibody fragment, dubbed VH Ab6, which can attach to that epitope found in all current SARS-CoV-2 variants.

“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’ve been looking for master keys – antibodies that continue to neutralize the virus even after extensive mutations.”

At this stage the research is still speculative. The antibody fragment demonstrated in the study is more there to demonstrate how broadly effective targeting this particular part of the spike protein could be in neutralizing all known variants.

So far there has been little mutational movement in the part of spike protein highlighted in this study. The researchers suggest future therapeutics for COVID-19 should target this specific epitope in the hopes of developing antibody treatments that can neutralize all variants of the virus.

Validating these new findings is another recent study demonstrating an antibody candidate that, so far, in animal studies, can neutralize all current SARS-CoV-2 variants. That study, published in Science Immunology, comes from a team of researchers at Harvard Medical School and Boston Children’s Hospital.

After genetically modifying mice so they would produce human-like immune responses to SARS-CoV-2, the researchers exposed the animals to parts of the virus and chronicled nine different groupings of antibodies. One specific antibody, dubbed SP1-77, was found to be incredibly potent at blocking infection from all known SARS-CoV-2 variants. And no prizes for guessing what part of the spike protein this variant-proof antibody targets.

“We now have a very clear picture of this vulnerable spot on the virus," said Subramaniam. "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. Having broadly effective, variant-resistant treatments would be a game changer in the ongoing fight against COVID-19.”

The new study was published in Nature Communications.

Source: University of British Columbia