Scientists from Scripps Research have discovered an anti-SARS-CoV antibody called CR3022 that was originally isolated in 2006 by Crucell Holland B.V., in the Netherlands. Previously, Chinese researchers suggested that CR3022 cross-reacts against SARS-CoV-2. Recently, Scripps Research evaluated how this antibody binds to SARS-CoV-2. The San Diego-based research institution vigorously pursues.
This antibody recovered from a survivor of the SARS epidemic in the early 2000s and revealed a potential vulnerability of the new coronavirus at the root of COVID-19, reports Scripps Research authors recently with their results published in Science.
This research, reports Scripps Research on their website, is the first to map a human antibody’s interaction with the new coronavirus at near-atomic-scale-resolution. It must be understood that this antibody was produced in response to an infection of SARS, which is caused by the SARS-CoV virus, however it cross-reacts with the new coronavirus, SARS-CoV-2. The structural mapping showcased a nearly identical site on both coronaviruses to which the antibody binds. This implies that a functionally important and vulnerable site for this family of coronaviruses.
Comments from the Wilson Lab
The Wilson lab, led by Ian Wilson, DPhil, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research, is known for its pioneering structural studies of antibodies bound to viruses including HIV and influenza. These studies have been used to inform designs of vaccines and antibody drugs, as well as other therapeutics.
Ian Wilson reports, “The knowledge of conserved sites like this can aid in the structure-based design of vaccines and therapeutics against SARS-CoV-2, and these would also protect against other coronaviruses—including those that may emerge in the future.” He continued, “Our ultimate goal here is to obtain structural information on antibodies and their binding sites, and use that to guide SARS-CoV-2 vaccine design, just as our lab has done with influenza and HIV” reports the study’s co-first author Nicholas Wu, PhD, a postdoctoral research associate at the Wilson lab.
The Wilson lab found that the antibody’s binding site is highly similar between the two coronaviruses—differing by just four protein building blocks called amino-acids. That high degree of similarity implies that the site has an important function that would be list if mutated significantly.
The Scripps Research analysis finds the antibody binding site is somewhat remote from the part of the virus that grabs hold of cell-surface protein receptors in preparation for penetrating cells in our lungs. This suggests that, at least for SARS-CoV, CR3002 neutralizes the virus’s ability to infect cells in some indirect way. Moreover, the antibody binding site is not normally accessible to antibodies.
Mysteries aside the findings point out that the binding site for this antibody on SARS-CoV-2 is a site of vulnerability. Perhaps if antibodies can bind to it tightly than the virus can be neutralized? If such neutralizing antibodies could be developed into therapies, then COVID-19 patients could be treated and this would be of great benefit to provide temporary protection from the virus to uninfected individuals such as healthcare workers.
More to Come?
As this binding site is highly conserved between SARS-CoV and SARS-CoV-2, there may be other antibodies yet to be discovered that can effectively neutralize both viruses—and perhaps in the same way, neutralize emergent coronaviruses before they can even cause pandemics?
This study was supported in part by the Bill & Melinda Gates Foundation and the National Institutes of Health.
- Ian Wilson, DPhil, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research
- Nicholas Wu, PhD, a postdoctoral research associate at the Wilson lab
- Meng Yuan, PhD, research associate
See the source for other researchers
Call to Action: Labs at Scripps Research and throughout the world are currently via blood donations, from people who have recovered from COVID-19 for further studies along these lines.