Small, antibody-like proteins known as VNARs (Variable New Antigen Receptors) are derived from the immune systems of sharks, and appear to be extremely potent in preventing COVID-19. According to a new study published in the journal Nature Communications, VNARs could effectively neutralize a large variety of coronaviruses, including SARS-CoV-2 and its most recent variants.
The shark proteins are ten times smaller than human antibodies and can bind to infectious proteins in unique ways that bolster their ability to stop infection.
“These small antibody-like proteins can get into nooks and crannies that human antibodies cannot access,” said study senior author Aaron LeBeau, a professor of pathology at the University of Wisconsin-Madison. “They can form these very unique geometries. This allows them to recognize structures in proteins that our human antibodies cannot.”
Professor LeBeau and his colleagues tested a large variety of shark proteins against both infectious SARS-CoV-2 and a version of the virus that cannot replicate in cells, and identified three candidate VNARs that rapidly and effectively stopped the virus from infecting human cells. When tested against SARS-CoV-1 (the virus causing the 2003 outbreak), the three VNARs also appeared to be highly effective.
One of the VNARs, called 3B4, attached strongly to a groove on the viral spike protein that is very similar among genetically diverse coronaviruses, allowing it to successfully neutralize even the MERS virus – a relatively distant cousin of SARS that led to an outbreak in 2012. This ability makes 3B4 an excellent candidate to fight viruses yet to emerge.
“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 Professor LeBeau.
Future therapies will probably include a cocktail of multiple shark proteins in order to optimize their effectiveness against a large array of different and mutating viruses. These drugs will be cheaper and easier to manufacture than human antibodies and could be delivered into the body through different routes.
Although they have not yet been tested in humans, they show an extraordinary therapeutic potential, particularly for people who do not respond well to vaccines and may need alternative protective strategies.