COVID-19: Scientists map powerful antibody
Scientists at the Fred Hutchinson Cancer Research Center in Seattle have shown that a potent antibody from a COVID-19 survivor interferes with a key feature on the surface of the coronavirus' distinctive spikes, causing critical pieces of the spikes to break off in the process.
A powerful antibody
This antibody - a tiny Y-shaped protein that is one of the body's main weapons against pathogens, including viruses - was isolated by Fred Hutch's team from a blood sample received from a patient in Washington State in the early days of the pandemic.
The team led by Drs. Leo Stamatatos, Andrew McGuire and Marie Pancera had previously reported that, among dozens of different antibodies naturally generated by the patient, CV30 was 530 times more potent than any of its competitors.
Using tools derived from high-energy physics, structural biologist Hutch Pancera and his postdoctoral researcher, Dr. Nicholas Hurlburt, have now mapped the molecular structure of CV30.
"Our study shows that this antibody neutralizes the virus by two mechanisms. One is that it overlaps the virus' target site on human cells, the other is that it induces the excretion or dissociation of part of the spike from the rest," said Dr. Pancera.
On the surface of this antibody's complex structure is a spot at the end of each of its flexible Y-shaped arms. This small piece of molecule can stretch neatly over a point on the coronavirus spike, a site that otherwise functions as a grappling hook to a docking site on human cells.
For prevention or treatment
The target of these brackets is the ACE2 receptor, a protein found on the surface of cells lining human lung tissue and blood vessels. But if antibodies such as CV30 cover these brackets, the coronavirus cannot easily bind to the ACE2 receptor. This weakens its ability to infect cells.
This highly effective antibody not only blocks the tip of the coronavirus spike, it apparently causes a part of the spike, called S1, to shear off. Hutch's researcher McGuire and his laboratory team conducted an experiment showing that in the presence of this antibody, there is a reduction in antibody binding over time, suggesting that the S1 section has sheared off the surface of the spike.
Fred Hutch's research team remains hopeful that the protein they discovered, CV30, could prove useful in the prevention or treatment of COVID-19. To find out, this antibody, along with other candidate proteins their team is studying, must be tested in pre-clinical and then human trials. "It's too early to know how effective they might be," said Dr. Pancera.
Translated with www.DeepL.com/Translator (free version)
