Lama antibodies appear to be able to neutralize the coronavirus SARS-CoV-2.

Worldwide, an effective treatment is currently being sought for COVID-19: the disease caused by the coronavirus SARS-CoV-2. British researchers are looking for such a treatment in an unexpected angle at first sight: with the llamas.

Antibodies bind to SARS-CoV-2
And successfully. Because in the journal Nature Structural and Molecular Biology they describe how they released the antibodies of llamas in the laboratory on the virus particles. The antibodies – after some adjustments – proved to bind excellently to the infamous spike protein of the virus. This protein uses the virus to enter human cells, but when antibodies bind to the protein, it no longer works. And so the antibodies basically harm the virus.

The researchers hope that the antibodies can eventually be used in the treatment of patients with a severe form of COVID-19. Perhaps they can stop the virus that is already wandering around in the body of patients and thus accelerate the recovery of the patients.

The surface of the coronavirus SARS-CoV-2 contains so-called ‘spikes’: proteins with which the virus can bind to the ACE 2 receptor and penetrate human cells. The new antibodies that researchers have now obtained thanks to llamas bind to these spike proteins, so that they can no longer bind to the ACE 2 receptor and so the virus is no longer able to invade human cells. Image: The Rosalind Franklin Institute.

Adapted antibodies
That researchers resort to llamas may sound a bit strange. But that is not it. Llamas – but also camels and alpacas – naturally produce small antibodies. These antibodies have a simpler structure than the antibodies of many other types of organisms and are therefore slightly easier to adjust. And that is exactly what the researchers have done to obtain antibodies that bind excellently to SARS-CoV-2. “We isolated antibodies that already bind – albeit fairly weakly – to the spike protein of the virus,” explains researcher Ray Owens to “Then we completely involuntarily changed a specific sequence in the antibodies that we expected to play a role in binding to the spike protein. And from those modified antibodies, we then selected the antibodies that bound much more strongly to the spike protein and which were found to neutralize it during laboratory experiments. ”

After these promising experiments, the researchers went one step further. They exposed the llama Fifi to harmless coronavirus proteins in the hope that they would make antibodies against the virus. And she did. “In tests, these antibodies were found to bind to the virus even better than the antibodies we adapted, so we are now working with these natural antibodies.”

If a treatment based on these antibodies is eventually developed, it will most likely consist of a cocktail of antibodies. “We were able to combine one of the antibodies (from the llamas, ed.) With a human antibody and demonstrated that the combination was even more potent than either of the antibodies alone,” said researcher James Naismith. A combination of different antibodies from llamas is also an option. “We see that our antibodies bind to different parts of the spike protein,” Owens explains to Scientias.nlfrom. “So by combining two or more, we expect to obtain a cocktail that is much more able to neutralize the virus than each antibody alone. We are still testing this idea. ”

Much work done in little time
Over the past few weeks, Owens and colleagues – encouraged by the urgent worldwide situation – have worked hard on the antibodies. “We created, analyzed and tested the antibodies in twelve weeks. Experiments that would normally take months to complete were completed in a few days. And we hope that we will make this breakthrough soon
can continue to pre-clinical experiments. ” During these experiments, the approach is tested among animals. “To date, we have demonstrated that the antibodies can neutralize the virus in the laboratory by preventing it from binding to human cells… To turn it into a potential treatment for COVID-19, we need to demonstrate that it also works in an animal model of the disease (ie a laboratory animal with SARS-CoV-2 or something similar to it, ed.). ”

On time?
So there is still some work to be done before clinical research can be considered: experiments in which the treatment is actually tested in humans. It raises the question whether these antibodies can be further developed quickly enough to make a difference during this pandemic. “Working towards testing among corona patients continues to be a high priority, but how long it takes is difficult to say,” Owens explains when asked. “However, it seems likely that COVID-19 will remain with us for a while.”

And so Owens and colleagues persist. “Our study – when it comes to preventing SARS-CoV-2 from infecting human cells – may have identified an Achilles heel of the virus. And that can help us not only identify clinically useful antibodies, but also develop vaccines that protect against viral infection. ”

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