Nanobodies that Block SARS-CoV-2 Spike Protein RBD Isolated

Researchers from NINDS have isolated a set of nanobodies against SARS-CoV-2. Preliminary results published in Scientific Reports today suggest that at least one of these nanobodies, called NIH-CoVnb-112, could prevent infections and detect virus particles by grabbing hold of SARS-CoV-2 spike proteins. In addition, the nanobody appeared to work equally well in either liquid or aerosol form, suggesting it could remain effective after inhalation.

Because nanobodies are more stable, less expensive to produce, and easier to engineer than typical antibodies, a growing body of researchers have been using them for medical research.  Since the pandemic broke, several researchers have produced llama nanobodies against the SARS-CoV-2 spike protein that may be effective at preventing infections. In the current study, the researchers used a slightly different strategy than others to find nanobodies that may work especially well.

“The SARS-CoV-2 spike protein acts like a key. It does this by opening the door to infections when it binds to a protein called the angiotensin converting enzyme 2 (ACE2) receptor, found on the surface of some cells,” said Thomas Esparza, the lead author of the study. “We developed a method that would isolate nanobodies that block infections by covering the teeth of the spike protein that bind to and unlock the ACE2 receptor.”

To do this, the researchers immunized a llama (Cormac) five times over 28 days with a purified version of the SARS-CoV-2 spike protein. After testing hundreds of nanobodies they found that Cormac produced 13 nanobodies that might be strong candidates.

Initial experiments suggested that one candidate, called NIH-CoVnb-112, could work very well. Test tube studies showed that this nanobody bound to the ACE2 receptor 2 to 10 times stronger than nanobodies produced by other labs. Other experiments suggested that the NIH nanobody stuck directly to the ACE2 receptor binding portion of the spike protein.

Then the team showed that the NIH-CoVnB-112 nanobody could be effective at preventing coronavirus infections. To mimic the SARS-CoV-2 virus, the researchers genetically mutated a harmless “pseudovirus” so that it could use the spike protein to infect cells that have human ACE2 receptors. The researchers saw that relatively low levels of the NIH-CoVnb-112 nanobodies prevented the pseudovirus from infecting these cells in petri dishes.

Image: Scientists isolated nanobodies against COVID-19 from a llama named Cormac.