In a significant development, scientists have identified a synthetic mini-antibody that turned out to be particularly effective in blocking the new coronavirus from entering human cells. The ability of SARS-CoV-2 to infect cells depends on interactions between the viral spike protein and the human cell surface protein ACE2.
To enable the virus to hook onto the cell surface, the spike protein binds ACE2 using three finger-like protrusions, called the receptor binding domains (RBDs).
The new synthetic mini-antibody blocks the RBDs, therefore has the potential to stop the virus from entering human cells, said the researchers from EMBL Hamburg, CSSB, Karolinska Institutet and University of Zurich.
EMBL Hamburg searched through the existing libraries to find sybodies that could block SARS-CoV-2 from infecting human cells.
Among the best binders, one called “sybody 23” turned out to be particularly effective in blocking the RBDs.
“Getting the results so quickly was only possible because the methodologies we used had already been established for other research projects unrelated to SARS-CoV-2. Developing these tools would have taken significantly more time and resources,” said Christian Low from EMBL Hamburg.
Nanobodies, small antibodies found in camels and llamas, are promising as tools against viruses due to their high stability and small size.
Although obtaining them from animals is time consuming, technological advances now allow for rapid selection of synthetic nanobodies, called sybodies.
A technology platform to select sybodies from large synthetic libraries was recently developed in the lab of Markus Seeger at the University of Zurich, and made available for this study.
The results hold out the promise of a potential way to treat COVID-19, the team said.
In future work, the scientists will perform further analyses to confirm whether sybody 23 could be an effective COVID-19 treatment.