Studying the crown of COVID-19 virus to find its weak point
SARS-CoV-2 Neutralizing Antibody
Diamond Light Source, the UK’s synchrotron, is providing priority rapid access for groups investigating SARS-CoV-2 proteins as part of the massive global scientific effort underway to find treatments or vaccines for SARS-CoV-2. The SARS antibody CR3022, by destroying the prominent spike proteins was shown to neutralize SARS-CoV-2 in the results published by one of these teams. Their work suggests that there could be a therapeutic potential of this antibody in combination with other antibodies or alone. For teams working to develop vaccines against SARS-CoV-2, their high-resolution data will also provide valuable structural data.
During the infection process, the spikes on SARS-CoV-2 serve two functions. First, the spikes on SARS-CoV-2 locks on to a human cell, and then, the outer membranes of the cell and the virus are merged as the spike undergoes a significant shape change. The virus can then reproduce in the human cell as its genetic material is easily transferred to the human cell.
At the point at which the virus would bind to a human cell, if the human immune system can produce antibodies that bind to the virus, the virus can be neutralized. Such an antibody working in this way is known as a receptor blocking antibody. Previously, it was thought that to neutralize the virus using antibodies, this would be the only way.
However, at the University of Oxford, the Head of Structural Biology at the Department of Clinical Medicine and the Director of Life Sciences at Diamond and one of the authors,
Prof. Dave Stuart explains, “this new research demonstrates that CR3022 works in an entirely different way. The team was able to watch the antibodies in action against the virus and to determine their method of attack using the high-resolution Cryo-electron microscopes at eBIC. It neutralizes the virus by destabilizing the spike protein entirely. Thus, CR3022 is a synergistic antibody, which could work in tandem with receptor-blocking antibodies, or on its own.”
He added, “This alternative method of attack could be particularly important in this antibody jigsaw puzzle. Many other useful antibodies that had previously been classed as ineffective could be identified with further screening. Human antibodies are relatively safe as they arise within the body. The antibodies could be quickly replicated in the quantities that would be needed by the drug companies.”
Viruses mutating so that antibodies no longer work is one of the ways in which viruses evade the immune system. However, in the case of the SARS-CoV-2 virus, the spike protein plays such an essential role that mutating it would be difficult, thus making it an excellent target for vaccines and treatments. To carry out macromolecular crystallography (MX) scans of the spike protein, the research team also used Diamond’s beamline I03.
“The protein crystals we produced leads to weak X-ray scattering as it had high levels of solvent. However, we got very high-quality data about the structure of the virus protein due to the high resolution we achieved with I03. As we may need to re-engineer the antibody to make it more effective, this kind of information is vital.”
Studying the crown of COVID-19 virus