From a llama named Cormac, researchers at the US National Institutes of Health (NIH) have isolated a set of tiny antibodies, or “nanobodies”, that hold promise against the novel coronavirus SARS-CoV-2. At least one of these nanobodies could prevent infections and detect virus particles by grabbing hold of SARS-CoV-2 spike proteins, the researchers suggest in the journal Scientific Reports. This nanobody, called NIH-CoVnb-112, appeared to work equally well in either liquid or aerosol form, which suggests it could remain effective after inhalation.
A nanobody is a special type of antibody naturally produced by the immune systems of camelids, a group of animals that includes camels, llamas, and alpacas. They are called nanobodies because they are tiny, about a tenth the weight of most human antibodies.
Because nanobodies are more stable, less expensive to produce, and easier to engineer than typical antibodies, 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, NIH said in a statement.
The spike protein acts like a key during coronavirus infection. It “unlocks” the door to infections when it binds to a human protein called ACE2 receptor on the cell surface. The NIH scientists developed a method that would isolate nanobodies that block infections by covering part of the spike protein that bind to and unlock the ACE2 receptor.
To do this, the researchers immunised 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 the nanobody 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, NIH said.
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.
Importantly, the researchers showed that the nanobody was equally effective in preventing the infections in petri dishes when it was sprayed through the kind of nebulizer, or inhaler, often used to help treat patients with asthma.
The team has applied for a patent on the NIH-CoVnB-112 nanobody, NIH said.