“It is another great example of how Elasmogen can effectively deliver potent therapeutic molecules.”įuture therapies would likely include a cocktail of multiple shark VNARs to maximize their effectiveness against diverse and mutating viruses. “What is exciting is that these new potential drug molecules against SARS-CoV-2 differ in their mechanism of action compared to other biologics and antibodies targeting this virus,” says Caroline Barelle, CEO of Elasmogen. However, this VNAR’s binding site is altered in some SARS-CoV-2 variants, which likely decreases its potency. The second-most-powerful shark VNAR, 2C02, seems to lock the spike protein into an inactive form. It’s a kind of insurance against the future.” “What we’re doing is preparing an arsenal of shark VNAR therapeutics that could be used down the road for future SARS outbreaks.
This research was conducted before the omicron variant was discovered, but initial models suggest the VNAR would remain effective against this new version, LeBeau says. The 3B4 binding site is also not changed in prominent variations of SARS-CoV-2, such as the delta variant. The ability to bind such conserved regions across diverse coronaviruses makes 3B4 an attractive candidate to fight viruses that have yet to infect people. This groove is very similar among genetically diverse coronaviruses, which even allows 3B4 to effectively neutralize the MERS virus, a distant cousin of the SARS viruses. One VNAR, named 3B4, attached strongly to a groove on the viral spike protein near where the virus binds to human cells and appears to block this attachment process. The three shark VNARs were also effective against SARS-CoV-1, which caused the first SARS outbreak in 2003. They identified three candidate VNARs from a pool of billions that effectively stopped the virus from infecting human cells. The researchers tested the shark VNARs against both infectious SARS-CoV-2 and a “pseudotype,” a version of the virus that can’t replicate in cells. This allows them to recognize structures in proteins that our human antibodies cannot.” “They can form these very unique geometries. “These small antibody-like proteins can get into nooks and crannies that human antibodies cannot access,” says LeBeau. One-tenth the size of human antibodies, the shark VNARs can bind to infectious proteins in unique ways that bolster their ability to halt infection. The anti-SARS-CoV-2 VNARs were isolated from Elasmogen’s large synthetic VNAR libraries.
The team published its findings in Nature Communications.Īaron LeBeau, associate professor in the Department of Pathology and Laboratory Medicine. LeBeau and his lab in the School of Medicine and Public Health collaborated with researchers at the University of Minnesota and Elasmogen, a biomedical company in Scotland that is developing therapeutic VNARs.
“The big issue is there are a number of coronaviruses that are poised for emergence in humans,” says Aaron LeBeau, a University of Wisconsin–Madison professor of pathology in the Carbone Cancer Center who helped lead the study. The shark VNARs were able to neutralize WIV1-CoV, a coronavirus that is capable of infecting human cells but currently circulates only in bats, where SARS-CoV-2, the virus that causes COVID-19, likely originated.ĭeveloping treatments for such animal-borne viruses ahead of time can prove useful if those viruses make the jump to people. The new VNARs will not be immediately available as a treatment in people, but they can help prepare for future coronavirus outbreaks. Small, unique antibody-like proteins known as VNARs - derived from the immune systems of sharks - can prevent the virus that causes COVID-19, its variants, and related coronaviruses from infecting human cells, according to a new study published Dec. Eric Lake of the Department of Pathology and Laboratory Medicine is part of a team that discovered new potential drug molecules against SARS-CoV-2 in sharks.
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