Antibody-like proteins developed from the immune systems of nurse sharks can prevent the SARS-CoV-2 virus that causes COVID-19 from infecting human cells, a University of Wisconsin researcher reports.
The new research, reported in the journal Nature Communications, could eventually yield therapies that are effective against mutating viruses like the Delta variant of SARS-CoV-2. The proteins are also effective against viruses that have yet to infect humans, including those that circulate in bats.
The small antibody-like proteins, called Variable New Antigen Receptors (VNARs), were able to neutralize WIV1-CoV, a bat coronavirus that is capable of infecting human cells.
“The big issue is there are a number of coronaviruses that are poised for emergence in humans,” said Aaron LeBeau, associate professor of pathology at the University of Wisconsin-Madison, 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.”
Nurse sharks are bottom-dwelling fish that prefer shallow, warm waters. They are slow swimmers with a reputation for being docile. They reach full size up to 10 feet long. Their mouths have rows of small sharp teeth for crushing shelled prey.
LeBeau’s lab at UW-Madison collaborated on the research with the University of Minnesota and the biomedical firm Elasmogen in Scotland. Researchers isolated the anti-COVID agents from Elasmogen’s library containing billions of VNARs. The shark VNARs are one-tenth the size of human antibodies and can bind to infectious proteins in unique ways, making them more effective at halting infections.
“These small antibody-like proteins can get into nooks and crannies that human antibodies cannot access,” LeBeau said in a statement released by the university. “They can form very unique geometries. This allows them to recognize structures in proteins that our human antibodies cannot.”
One of the shark VNARs attached strongly to the SARS-CoV-2 viral spike protein, near where the virus binds to human cells—and appeared to block the attachment process. The “groove” on the spike protein is similar to those found on other coronaviruses, allowing the VNARs to neutralize the MERS virus, a cousin of SARS viruses.
Another VNAR appears to lock the spike protein in an inactive form. The binding site on this VNAR is altered on some variants of the SARS-CoV-2 virus, likely decreasing its potency, LeBeau said.
Eventual therapeutics could include a “cocktail” of multiple shark VNARs to maximize their effectiveness against diverse and mutating viruses, the university said. This class of drugs would be less expensive and easier to manufacture than human antibodies.