Researchers from the University of Wisconsin-Madison showed that the 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 likely originated.
“The big issue is there are a number of coronaviruses that are poised for emergence in humans. 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,” said Aaron LeBeau, Professor of pathology at the varsity.
“These small antibody-like proteins can get into nooks and crannies that human antibodies cannot access. They can form these very unique geometries. This allows them to recognize structures in proteins that our human antibodies cannot,” LeBeau said. The team published its findings in the journal Nature Communications.
In the study, 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 3B4 binding site is also not changed in prominent variations of SARS-CoV-2, such as the delta variant. This research was conducted before the Omicron variant was discovered, but initial models suggest the VNAR would remain effective against this new variant, LeBeau said.
The second-most-powerful shark VNAR, 2C02, seems to lock the spike protein into an inactive form. However, this VNAR’s binding site is altered in some SARS-CoV-2 variants, which likely decreases its potency.
Future therapies would likely include a cocktail of multiple shark VNARs to maximize their effectiveness against diverse and mutating viruses. LeBeau is also studying the ability of shark VNARs to help in the treatment and diagnosis of cancers.