Millions of years Previously, some unknown common ancestors of today’s lamas, camels and alpacas went through an unusual genetic mutation. This evolutionary event gave the lamas and their kin a strange type of antibody that no other mammals possess – which could surprisingly aid the fight against Kovid-19. This Monday, in the magazine Nature structural and molecular biologyResearchers at the Rosalind Franklin Institute and the University of Oxford report the discovery of antibodies to two lamas, also known as “nanobodies”, that can inhibit the virus Kovid-19 infects human cells.
“these [nanobodies] Can block – powerfully inhibit interactions between the virus and the human cell, ”says Ray Owens, a professor of molecular biology at the University of Oxford and one of the study’s senior authors. “They basically neutralize the virus.”
Like all antibodies, the nanobodies that Ovens and his team have developed have the ability to detect and attach to a specific location on a specific protein – in this case, the so-called “spike protein” that forms the surface of a novel coronavirus Let’s cover. When these spikes tick ACE2, a protein that sits outside of many human cells, the coronavirus can enter and infect those cells. If, however, the spike protein is blocked from attaching to ACE2, the virus will float harmlessly, unable to invade.
Most species, including humans, produce very similar antibodies. Typically, antibodies developed for medical treatment are first produced in laboratory animals such as rabbits, then isolated and genetically linked more closely to human antibodies. But some species, including llamas, their companion camels and sharks, are antibody oddballs. These animals make nanobodies, so they are called because they are much smaller than their antibody cousins.
These small molecules have their own special benefits. “Sometimes there may be a special pocket that forms on the surface of a protein that is recessed,” Jason McClellan, an associate professor of molecular biosciences at the University of Texas at Austin who also discovered a llama nano that spikes proteins Blocks. Binding to ACE2. Large antibodies, he says, “cannot bind inside that pocket.”
Even when they are used in exactly the same spots, nanobodies can have an edge over human antibodies. “They are very stable,” Owens says. Unlike most antibodies, they maintain their shape in extreme environments like the human stomach.
Given these advantages, nanobodies have been developed as a treatment for diseases, and one has been approved by the FDA as a treatment for cancer. The tried and true method of developing nanobioids involves injecting a harmless chunk of a germ into a llama and waiting for the animal to mount an immune response. But vaccinating a llama and removing its nanobodies is a long-drawn process, slower than Kovid-19-era research standards. Hence Owens and his colleagues signed a separate deal.
He began with a huge set of nanobodies, previously separated from the Lamas. “We have a complete collection of different scenes with different binding capabilities,” says Owens. They then used the spike protein to “fish out” any nanobodies it would attach to. This strategy allowed them to quickly identify a nano potentially against SARS-CoV-2.
Unfortunately, none of this protein was sufficiently attuned to effectively block novel coronaviruses from entering cells. So Owens and his team randomly linked the sphere protein to the nanocle region in hopes of making a snug fit. And they succeeded: in the presence of a large amount of one of these mutated nanobodies, SARS-CoV-2 was completely unable to enter human cells. “They literally can’t develop the infection,” Owens says.