Shark Antibody-like Proteins Neutralize COVID-19 Virus

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.

From: University of Wisconsin, Madison

December 17, 2021 --The new VNARs will not be immediately available as a treatment in people, but they can help prepare for future coronavirus outbreaks. 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.

Developing treatments for such animal-borne viruses ahead of time can prove useful if those viruses make the jump to people.

"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 who helped lead the study. "What we're doing is preparing an arsenal of shark VNAR therapeutics that could be used down the road for future SARS outbreaks. It's a kind of insurance against the future."

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 team published its findings in Nature Communications.

The anti-SARS-CoV-2 VNARs were isolated from Elasmogen's large synthetic VNAR libraries. 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.

"These small antibody-like proteins can get into nooks and crannies that human antibodies cannot access," says LeBeau. "They can form these very unique geometries. This allows them to recognize structures in proteins that our human antibodies cannot."

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. They identified three candidate VNARs from a pool of billions that effectively stopped the virus from infecting human cells. The three shark VNARs were also effective against SARS-CoV-1, which caused the first SARS outbreak in 2003.

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. 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.

The ability to bind such conserved regions across diverse coronaviruses makes 3B4 an attractive candidate to fight viruses that have yet to infect people.

           https://www.sciencedaily.com/releases/2021/12/211217102915.htm