New targets for COVID-19 antibodies have been identified, demonstrating new opportunities to fight the virus.
Each person infected with COVID-19 has the potential to create antibodies that target the virus in a slightly different way due to the way antibodies are made. Analysing these different sets of antibodies can provide the opportunity to find different ways of neutralising the virus.
In the most comprehensive study of its kind to date, an international team of researchers has examined the antibodies from a large cohort of COVID-19 patients, finding that there is an opportunity to attack the virus using different antibodies over a much larger area.
The research has been published in the journal Cell.
New ways to attack the virus
The research team has built a comprehensive and detailed map of where each antibody attaches to the receptor binding domain by studying the interaction of the antibodies with the viral spike protein.
The map shows that the majority of strong, COVID-19 neutralising antibodies overlap the binding site for the receptor and revealed common modes of attachment for potent antibodies that are shared by many people, helping the team understand how to target the virus in the future.
Professor Sir Dave Stuart, Life Sciences Director at Diamond and Joint Head of Structural Biology at the University of Oxford, said: “SARS CoV-2 is the virus that causes COVID-19. Once infected with this virus, the human immune system begins to fight the virus by producing antibodies. The main target for these antibodies is the spike protein that protrudes from the virus’s spherical surface. The spike is the portion of the virus that interacts with receptors on human cells. This means that if it becomes obstructed by antibodies, then it is less likely that the virus can interact with human cells and cause infection.
“By using Diamond Light Source, applying X-ray crystallography and cryo-EM, we were able to visualise and understand how antibodies interact with and neutralise the virus. The study narrowed down the 377 antibodies that recognise the spike to focus mainly on 80 of them that bound to the receptor binding domain of the virus, which is where the virus spike docks with human cells.”
In animal models, the team found that the most neutralising antibodies could be used ahead of infection to prevent disease and as a therapeutic treatment when an infection is already in progress, which could potentially reduce the severity of the infection and decrease recovery times.
Dr Helen Ginn, Post-Doctoral Research Assistant at Diamond Light Source added: “The receptor binding domain resembles a human torso. During this extensive study on 80 antibodies, we have discovered weak points at five different areas on the torso. The weak points can be found running between the left shoulder and neck, on the right shoulder, down the right flank and on the left flank.”
The team hope this novel mapping method can provide vital information to fight the virus and be used to provide roadmaps for understanding weakness in other viral diseases.
