How Shark Antibodies Could Aid the Fight Against Coronavirus and Prepare for Future Outbreaks

The protein-like immune molecules were found to block SARS-Cov-2 from entering human cells

An image of two small nurse sharks in a pool
Sharks have been on the planet for close to 500 million years and, in that time, have developed an extraordinary immune system with immune mechanisms that mammals do not have.
  Bryce Richter

Nurse sharks (Ginglymostomatidae) are slow-moving, bottom-dwelling predators that stalk prey in warm shallow waters of the Atlantic and Pacific oceans. In a new study published in Nature Communications, scientists suggest the sharks could lend a fin in a new, more effective treatment for Covid-19.

Researchers found that tiny antibodies found in the sharks' blood may prevent SARS-CoV-2, the virus that causes Covid-19, and its variants from entering and infecting human cells, reports Mark Johnson for the Milwaukee Journal Sentinel.

The results could help scientists prepare for future outbreaks of animal-borne viruses that make the jump to humans. The study may provide insight into how to build immunity against viruses without vaccination in those who are immunocompromised and do not respond well to vaccination, per a University of Wisconsin–Madison statement.

The miniature, antibody-like proteins are known as Variable Antigen Receptors (VNARS). They are among the smallest naturally-occurring binding domains found in nature. Shark VNARS are one-tenth of the size of human antibodies. VNARS bind to viral proteins in a way that prevents infection, per a statement.

"The big issue is there are a number of coronaviruses that are poised for emergence in humans," study author Aaron LeBeau, a pathologist at UW-Madison, says in a statement. "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."

Sharks have been on the planet for close to 500 million years and, in that time, they have developed an extraordinary immune system with defense mechanisms that other mammals do not have, per the Journal Sentinel.

First discovered by researchers at the Free University of Brussels in the 1980s, the sharks' antibodies are tiny with a distinctive shape that allows them to tightly pack together and block the coronaviruses from latching onto human cells. For this reason, immunologists are studying shark antibodies for future use in immunotherapeutic settings and could be used to treat cancers and develop new drugs. These antibodies are also found in llamas, alpacas, and camels.

An image of four graduate students standing near a pool with a nurse shark swimming against the pools wall. Each student is wearing a lab coat, gloves and a mask.
The nurse sharks are kept in large pools on a UW-Madison campus lab aquarium.
  Bryce Richter

Antibodies taken from the nurse sharks' immune systems were effective against the coronavirus and its variants in laboratory trials using human lung and embryonic kidney cells. The researchers found that the antibodies block the virus from entering cells by preventing the spike protein from gripping onto the ACE2 receptor on human cells, reports the Milwaukee Journal Sentinel.

In collaboration with experts at the University of Minnesota and Elasmogen, a Scottish biotech firm working on therapeutic VNARs, the team tested shark VNARs against the infectious SARS-Cov-2 and a pseudotype that does not replicate cells, a statement explains. From a list of billions of VNARS, researchers identified three that stopped SARS-Cov-2 from entering human cells.

One of these VNARS included 3B4, which bonded to the viral spike protein near where SARS-Cov-2 binds to human cells. This binding location on the viral spike protein is common in other kinds of coronaviruses and could be targeted to fight viruses that have yet to jump to humans. The 3B4 binding site is also found in variants of SARS-Cov-2, like Delta.

While the antibodies belong to sharks, LeBeau says they are similar enough to human antibodies that rejection is unlikely, per the Journal Sentinel. However, because the shark's antibodies are so small, introducing them to a Covid-19 patient may not be as effective because they would be filtered out through the kidneys faster than human antibodies, reports Toni Galli for WKOW. In turn, patients would not have enough time to fully reap the benefits to build immunity.

LeBeau told WKOW that teaming with Elasmogen may mean human trials and the development of a shark antibodies treatment could happen as early as two years. Before they even reach human trials, the shark antibodies need to be tested in rats or mice to determine safety. Then, the antibodies will be tested in non-human primates if they pass this process. If everything checks out from there, the shark antibodies would be ready for a Phase I clinical trial in humans, the Journal Sentinel reports. 

"We think they're the next big thing," LeBeau tells the Journal Sentinel. "This is the first paper to show their effectiveness against an infectious disease."

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