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Llamas to the Rescue! Can Fifi, Rocky, and Marley Save Us from COVID-19?

This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. CDC

Although they’re pretty dang adorable, llamas are known for being fierce protectors of flocks of sheep—even taking out a hungry coyote here and there. Now, it seems that the cute camelids might be able to help humans as well in our fight against COVID-19 thanks to some pretty special antibodies.

Llamas have been studied since the early 1990s for their ability to produce antibodies that are smaller and less complicated than those produced by humans. The particles are so small, in fact (up to one-tenth the size of normal antibodies), that they are termed nanobodies. In early 2019, the Food and Drug Administration approved the first llama-derived nanobody treatment called caplacizumab-yhdp (try saying that five times fast) for adult patients with acquired thrombotic thrombocytopenic purpura, a rare but highly destructive blood disorder. 

Warheads From Rocky and Marley

Since early March, researchers at the Rockefeller University in New York have been working with two llamas named Rocky and Marley to find out how their unique antibodies might help blast the SARS-CoV-2 virus. 

“For reasons that we don’t really understand, these animals make this variant of antibody that just has fantastic properties,” said Michael P. Rout, a structural biologist at Rockefeller. “It contains the good disease-recognizing parts of a human antibody, packed into a condensed warhead.”

Unlike human antibodies, which consist of two proteins, llama antibodies only have one protein. This not only makes them small, but much easier to replicate and test. It might make any potential treatments easier to take because they could eventually be nebulized and distributed in the same way inhalers disperse asthma medicine. 

The small size of these particles also makes them easy to combine, a benefit UK researchers have just taken advantage of.

Human/Llama Hybrid

The team reporting the discovery in the journal Nature Structural & Molecular Biology consists of scientists from the Rosalind Franklin Institute, Oxford University, Diamond Light Source, and Public Health England. They used advanced imaging consisting of X-rays and electrons to see that llama-derived antibodies bind to the spikes on the SARS-CoV-2 virus in a way that’s different than other antibodies that have been tested so far. 

“The electron microscopy structures showed us that the three nanobodies can bind to the virus spike, essentially covering up the portions that the virus uses to enter human cells,” said Professor David Stuart, from Diamond Light Source and Oxford University.

 By blanketing the virus and dulling its spikes, the antibodies prevent virus particles from landing on and penetrating human cells.

 What’s more, the researchers found that when combining the llama nanobodies with human antibodies, the treatment resulted in even greater results.

 “These nanobodies have the potential to be used in a similar way to convalescent serum, effectively stopping progression of the virus in patients who are ill,” said professor James Naismith, Professor of Structural Biology at Oxford University. “We were able to combine one of the nanobodies with a human antibody and show the combination was even more powerful than either alone. Combinations are particularly useful since the virus has to change multiple things at the same time to escape; this is very hard for the virus to do. The nanobodies also have potential as a powerful diagnostic.”

Fifi Factory

Now the team is working with a llama named Fifi. They’ve injected her with purified virus proteins that don’t cause disease or harm but activate’s Fifi’s immune system. Thus far, Fifi is acting like an antiviral production facility, as her blood churns out even more antibodies than already discovered.