A synthetic nanobody could be used to help combat COVID-19, a new study has revealed.
It is believed that blocking three receptor binding domains (RBDs), which the SARS-CoV-2 virus hooks on to, could stop it from entering human cells.
The Christian Löw group at the European Molecular Biology Laboratory (eMBL) Hamburg, Germany, searched through the existing libraries to find synthetic nanobodies, called sybodies, that could block SARS-CoV-2 from infecting human cells.
They used the viral spike protein’s RBDs as bait to select those sybodies that bind to them before testing the selected sybodies according to their stability, effectiveness, and the precision of binding.
They found that sybody 23 was particularly effective in blocking the RBDs.
Researchers in the Dmitri Svergun group at EMBL Hamburg carried out small-angle X-ray scattering n to analyse the binding of sybody 23 to the RBDs, while Martin Hällberg at the Centre for Structural Systems Biology (CSSB) and Karolinska Institutet, Sweden, used cryo-EM to determine the structure of the full SARS-CoV-2 spike that bound to sybody 23.
Normally, RBDs switch between the ‘up’ position, ready to bind ACE2, or in the ‘down’ position, when they become furled to hide from the human immune system.
The researchers found that the molecular structures revealed that sybody 23 binds RBDs in both ‘up’ and ‘down’ positions and blocks the areas where ACE2 would normally bind.
They believe the ability to block RBDs regardless of their position might explain why sybody 23 is so effective.
Ben Murrell and his team at Karolinska Institutet tested to see if sybody 23 can neutralise a virus by using a lentivirus that was modified to carry the SARS-CoV-2’s spike protein on its surface.
They found that sybody 23 successfully disabled the modified virus in vitro, although further tests are needed to see if it could stop SARS-CoV-2 infection in the human body.
Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2. Nature Communications 4 November 2020
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