Despite a primitive immune system, sharks have a natural immunity to viruses that afflict other living creatures. Researchers are finding out why. A chemical compound -- unknown elsewhere -- found in the tissue of dogfish sharks can be used to combat human viruses, according to scientists.
The compound, known as squalamine, is found in the liver of the shark and can be used to treat a broad range of diseases from dengue and yellow fever to hepatitis B, C and D.
Scientists were already aware that the predator produces squalamine which it uses to fight off bacteria. But more recent research led to the discovery that the shark extract works in a completely new way that could make it an effective antiviral drug, say the researchers.
To realize that squalamine potentially has broad antiviral properties is immensely exciting, especially since we already know so much from ongoing studies about its behavior in people, said lead author Dr. Michael Zasloff of Georgetown University.
Since the chemical has already been used in human clinical trials to stop blood vessel growth in cancers and to prevent eye disorders, it could be quickly tested as a new treatment for viral diseases, researchers at Georgetown University Medical Center said.
Zasloff and his colleagues discovered squalamine almost two decades ago while studying sharks in hopes of finding new, naturally occurring antibiotic agents.
I was interested in sharks because of their seemingly primitive but effective immune system. No one could explain why the shark was so hardy, said Zasloff, reports the Daily Mail.
On studying the compound, Zasloff found that it prevented the growth of rapidly growing blood vessels, such as those found in tumor growth and certain retinal diseases.
To test the theory that squalamine had antiviral properties, he sent samples of the compound -- now synthesized in the lab without shark tissue -- to viral researchers across the country, reports WebMD.com.
Laboratory and animal studies confirmed that the chemical had unambiguous activity against viruses that attack cells in the liver and blood, including those that cause hepatitis B, C and D, yellow fever and dengue fever, said Zasloff, according to the report.
Zasloff explained that instead of targeting the viruses directly, squalamine protects the cells that line the blood vessels and liver from infection. Squalamine, which is a positively charged molecule, sticks to the cell's inner membranes, which have negative charges. As a result squalamine kicks off positively charged proteins that are bound to the negatively charged surface of the cell's inner membrane. When a virus invades a cell, it expects those proteins to be present on the cell membrane. Without them, the virus can't reproduce.
To me, the key to squalamine is that once in the body it times its action to match the life cycle of most viruses.
Most viruses take hours to complete their life cycle, the same period in which squalamine renders tissues and organs viral resistant after administration.
In addition, it acts fast to stop viral replication, clearing the body of these predators within hours.
Furthermore, because squalamine acts by making the host's tissues less receptive for infection, rather than by targeting a specific viral protein, the emergence of viral resistance would not be anticipated, said Zasloff, the Daily Mail reports.
In the study, some of the experiments were conducted in tissue culture cells of various types: human liver cells for the hepatitis viruses and human blood vessel cells for the dengue virus. In other cases, such as yellow fever and cytomegalovirus, the tests were done in hamsters and mice. Some of the animals recovered from the infections.
According to a National Geographic report, current squalamine compounds can access only cells that have chemical portals to permit its entry, such as those in blood vessels, capillaries and the liver. But a squalamine-based drug could potentially be tailored to fight a wide variety of viruses in other types of cells, said Zasloff.
Zasloff believes that even though all substances have some toxicity, clinical trials would reveal how safe the drug is for humans. He predicts clinical trials for the antiviral will begin in people in about a year.
The study was published in the journal Proceedings of the National Academy of Sciences.
We may be able to harness the shark's novel immune system to turn all of these antiviral compounds into agents that protect humans against a wide variety of viruses. That would be revolutionary, said Zasloff. While many antibacterial agents exist, doctors have few antiviral drugs to help their patients, and few of those are broadly active.