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Shark antibodies used in new antiviral therapies

Scientists found therapeutics derived from shark antibodies are effective in treating emerging variants of COVID-19 and related viruses.

Image Credit: Photo by Alexandre Boucey on Unsplash

Since the world experienced the shock of the novel coronavirus in 2019, the original virus has repeatedly evolved into new variants. New variants of viruses like COVID-19 can become unrecognizable to our immune system, meaning even people that have been vaccinated against them can get infected. Scientists therefore want to find new methods to stay at least one step ahead of these viruses.

Researchers have previously developed treatments for COVID-19 that block the virus from entering a healthy cell. The virus enters the cell when part of its outer layer, called the spike protein, attaches to a docking station on the cell. These docking stations are found on many different types of human cells, such as the lungs, kidneys, stomach, liver, blood vessels, and heart. Alternative treatments like these can be effective in stopping the spread of viruses when used alongside vaccines. 

Another important interaction that counteracts the spread of viruses occurs between proteins produced to fight a virus, called antibodies, and ID tags found on the surfaces of viruses, called epitopes. New therapies, called neutralizing antibody (NAb) therapies, neutralize COVID-19 by releasing antibodies that attach to epitopes on the spike protein, blocking it from attaching to a healthy cell. 

Scientists have already shown NAb therapies can be effective against COVID-19, but they also have limitations. The spike protein is prone to rapid mutation, meaning its epitope can become unrecognizable to human antibodies and current NAb therapies. As a result, NAb therapies can sometimes miss variants of COVID-19 with a new epitope. This mistaken identity lets the virus infect healthy cells. 

Scientists are looking to the animal kingdom for further help in dealing with new viral variants. Researchers have found the size of antibodies are highly variable between different animal species. Smaller antibodies are better than bigger antibodies at neutralizing foreign pathogens, because they can recognize smaller epitopes that bigger antibodies cannot. Large antibodies like the ones produced by the human immune system can sometimes allow viruses to go under the radar and infect healthy cells.

The smallest antibodies in nature are found in sharks, so an international group of scientists set out to uncover if shark antibodies can help combat COVID-19 variants. The team first tested whether shark antibodies could neutralize COVID-19. They did this by mixing different strains of COVID-19 with a set of shark and human antibodies, then measuring how well the virus was neutralized. The scientists found the shark antibodies were able to neutralize many different strains. 

Next they used X-rays to view the molecular interaction between the shark antibodies and the viruses. They found these antibodies neutralized the COVID-19 particles in a different way than the human antibodies did. In particular, the shark antibodies blocked the spike protein by pinning it down in a specific shape. 

To visualize how effective the shark antibodies were at neutralizing COVID-19, the scientists stained COVID-19 molecules with a fluorescent protein. They tracked the concentration of these viral molecules in chambered plates with human antibodies and shark antibodies by measuring the amount of fluorescence that was emitted over a period of time. They showed the concentration of viral molecules rapidly decreased when shark antibodies were present. The scientists suggested shark antibodies interact with an epitope that human antibodies don’t recognize, although it’s found in many related strains and viruses.  

These researchers concluded shark antibodies are effective against new COVID-19 variants and related diseases. The team suggested antibody therapeutics could continue to become smaller and smaller, but remain just as effective. They proposed the development of new antibody therapies, along with vaccines and current NAb therapeutics, to help control the spread of new viruses. 

Study Information

Original study: Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography

Study was published on: December 16, 2021

Study author(s): Obinna C. Ubah, Eric W. Lake, Gihan S. Gunaratne, Joseph P. Gallant, Marie Fernie, Austin J. Robertson, Jonathan S. Marchant, Tyler D. Bold, Ryan A. Langlois, William E. Matchett, Joshua M. Thiede, Ke Shi, Lulu Yin, Nicholas H. Moeller, Surajit Banerjee, Laura Ferguson, Marina Kovaleva, Andrew J. Porter, Hideki Aihara, Aaron M. LeBeau, Caroline J. Barelle

The study was done at: University of Aberdeen (UK), Elasmogen Ltd. (UK), University of Wisconsin (USA), Medical College of Wisconsin (USA), University of Wisconsin (USA), University of Minnesota (USA), Cornell University (USA)

The study was funded by: Chief Scientist Office, Scottish Government

Raw data availability: Data available upon request.

Featured image credit: Photo by Alexandre Boucey on Unsplash

This summary was edited by: Gina Misra and Aubrey Zerkle