Antibody could provide comprehensive protection against evolving SARS-CoV-2 virus

Researchers at Northeastern University say they have discovered that an antibody could provide broad protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19 — even as the virus evolves to outsmart the body's other chemical defenses.

Researchers studied the structure of SARS-CoV-2's spike protein – the outer extensions of the virus's membrane that are responsible for the virus's entry into a human cell. After the COVID-19 pandemic broke out, scientists quickly figured out how the spike protein helps the virus attach to a cell by binding to an enzyme called the ACE-2 receptor.

But it was only when researchers examined the structure of the spike protein that they learned more about its limb-like construction: These protruding strands rearrange themselves when they “pull” a cell toward them and initiate fusion.

“For infection to occur, the spike protein has to jump out and grab a human cell,” says Paul Whitford, associate professor of physics at Northeastern University, who co-led the theoretical aspects of the study, which Science.

What the researchers showed was that a specific antibody – known as CV3-25 – disrupts the cell infection process by attacking a specific site on the spike protein that is largely conserved across different virus strains, the study said.

The receptor binding domain, the critical part of the spike protein that allows the virus to “attach” and eventually enter the cell, typically changes as the virus evolves, Whitford says. The region that often stays the same is vulnerable to CV3-25.

Think of it as the Achilles heel of the virus.

The results suggest that the broadly neutralizing antibody could be the key to creating a vaccine that protects against a rapidly evolving virus.

“This is a naturally occurring antibody that has been found in samples taken from humans,” says Whitford.

The computational work was a joint effort between Northeastern University's Center for Theoretical Biological Physics and Rice University, a National Science Foundation Physics Frontiers Center. The multi-university team also collaborated with a group of researchers at Yale University as part of the overall study.

Whitford's expertise lies in using theoretical models to study “large molecular assemblies” – chemical structures that include viruses and their surface structures. In the vast world of the infinitely small, Whitford has focused primarily on studying the workings of the ribosome, a biomolecular machine responsible for producing the proteins that make up living organisms.

Earlier this month, U.S. health officials declared that COVID-19 was no longer a pandemic but was now “endemic.” That means the virus will likely continue to circulate, only it is now well under control. But Whitford says there could still be more contagious and potentially deadly variants of the virus.

“It's still a very big problem, but one that can now be managed against the backdrop of many public health threats rather than as some sort of singular pandemic threat,” Aron Hall, deputy director for science in the Centers for Disease Control and Prevention's Division of Coronaviruses and Other Respiratory Viruses, said recently, according to NPR. “And so our approach to COVID-19 is very similar to how we approach other endemic diseases.”

The results are important because scientists have not yet succeeded in developing a vaccine that protects against all current and future variants of the virus, Whitford says.

“We currently have the virus under control, but it is constantly mutating,” says Whitford.

Whitford says the antibody could be “the next big target” in developing new vaccines.

“It opens up a new vaccination strategy,” he says. “While current vaccines try to block the arms, our results show how to shackle the legs instead, giving us a new weapon in the fight against this ever-changing virus.”

This story is republished with permission from Northeastern Global News news.northeastern.edu.