Tightly twisted core of stem of SARS-CoV-2 spike protein made its variants fit: Study

New Delhi, April 3 (PTI) A ‘tighter’ core of the stem of the SARS-CoV-2 spike protein could be the reason for the enhanced fitness of the virus’s mutant strains, according to a new research.

Researchers from Pennsylvania State University, US, said that the Omicron variant’s stem is as rigid as it can get. This could mean, they said in a study, that newer vaccines may be effective for longer than the ones targeting the original variant.

“We found that the spike protein was initially more flexible at the stem region, which is where the spike protein is bundled together, but over time, mutations caused the protein to become progressively tighter and more rigid, and we think it’s now as rigid as it can get,” said Ganesh Anand, study author and associate professor of chemistry and of biochemistry and molecular biology, Penn State.

The study is published in the journal eLife.

A technique called amide hydrogen/deuterium exchange mass spectrometry was used to study how the spike protein changed with each of the new variants.

Explaining the structure of the SARS-CoV-2 spike protein, Anand said that it is composed of three chain molecules called monomers that are bound together to form a trimer. Two subunits, S1 and S2 make up the spike protein, with S1 containing a receptor binding domain, and S2 containing the stem region bundling the trimer.

“It is analogous to a tree, with the stem forming the trunk and the receptor binding domain forming the branches,” said Anand.

The study revealed that the stem first stiffened with the D614G mutation common to all SARS-CoV-2 variants. The stem progressively twisted with each mutation in subsequent variants, with the Omicron BA.1 variant exhibiting the largest magnitude increase in stabilization.

“We can say that the changes likely made the virus more fit, which could translate to better transmission,” said Anand.

“A tighter core could likely make the virus more stable in nasal droplets and faster at binding to and entering host cells. So, for example, what initially took about 11 days to develop an infection after exposure now takes only about four days,” said Anand.

Having been generated against the spike protein of the original wild-type variant, Anand said that the vaccines, thus, have not been able to fully neutralise the virus.

“The latest bivalent booster targeting newer variants helps, but people who never got this booster aren’t receiving this more targeted protection,” he said.

“Future vaccines that focus specifically on Omicron are likely to be effective for longer,” said Anand.

Anand said that the spike protein has now become so tightly twisted that it is unlikely to structurally change further at the stem region.

“There are limits to how much it can tighten,” he said. “I think that we can have some cautious optimism, in that we’re not going to continuously have variants emerging, at least tightening is not going to be a mechanism.”