Are Sharks the Answer to the Flu Virus?

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The shark steroid Squalamine has recently been shown to be a potent virus fighting agent in animal studies. Squalamine demonstrates a therapeutic ability to protect man from viral diseases such as dengue and yellow fever as well as hepatitis B, C and D. Scientists discovered that its mechanism of action is to displace proteins along the inner cell wall that viruses need in order to replicate after infection.

Animals, like humans require an immune system of sorts for protection against the myriad types of disease-causing organisms. The gut of an animal is one arena where the fight against infection plays an important role in health. In fact, it was the gut of a species of frog where scientists previously discovered antibiotic substances that fought off environmental microbes that had been ingested during feeding.

This discovery led scientists to look at the guts of several species, one of which was a species from the genus Squalidae (“Squalus” is Latin for shark) that is commonly known as the “dogfish shark.” Scientists chose the shark as an animal to look for antibiotic substances because it is considered a primitive animal and is believed to have an early type of immune system. The shark fossil record dates the modern shark as far back as 400 million years ago with little evolutionary change. Sharks are among the few species referred to as living fossils.

Dogfish sharks are relatively small ranging in size from 19 to 60 inches. They are carnivorous, but not known to attack humans. Unlike other shark species, the dogfish shark has a dorsal spine that carries a mildly toxic venom.

In 1992 scientists reported that the dogfish shark possess a gut defense system with a potent antimicrobial steroid that can destroy a wide range of disease causing organisms such as fungi, protozoans, and both gram-positive and gram-negative bacteria.

They named the steroid “squalamine” after the genus name “Squalus” and the chemical structure “amine” and classified squalamine as a naturally- occurring broad-spectrum antibiotic of animal origin. Squalamine was later found to have pharmacological activity that inhibited several growth factors involved in new blood vessel formation and was proposed to be potentially useful toward treating some forms of cancer.

More recently, in a paper published in the Proceedings of the National Academy of Sciences (PNAS), scientists discovered that squalamine enters animal cells and binds to the inner cell wall due to an electrostatic charge difference between squalamine and the cell wall. When this happens, they found that squalamine causes membrane-anchored proteins on the inner cell wall to be displaced. Some of these proteins are needed by viruses in order to replicate upon infection. With the proteins no longer attached to the cell wall, virus replication is prevented, which thereby essentially stops the virus in its tracks and prevents further viral production and infection of neighboring cells.

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According to the study’s lead investigator, Michael Zasloff, M.D., Ph.D., professor of surgery and pediatrics at Georgetown University Medical Center and scientific director of the Georgetown Transplant Institute, "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," Zasloff says. "That would be revolutionary. While many antibacterial agents exist, doctors have few antiviral drugs to help their patients, and few of those are broadly active."

To further test squalamine’s effectiveness against a broad range of viruses, Dr. Zasloff sent samples of squalamine to other researchers around the country who work with a variety of viruses. What they found was that in human tissue culture, squalamine inhibits infection by the dengue virus as well as viral hepatitis B and D. Animal studies also showed that squalamine can control viral infections in yellow fever, eastern equine encephalitis and murine (mouse) cytomegalovirus. In some cases, squalamine treatment even cured the infected animals.

The results of their paper states that squalamine unambiguously demonstrates an active role in both cell culture and animal studies against a broad spectrum of human viral pathogens, including both RNA- and DNA-enveloped viruses. “We believe that squalamine exerts its antiviral effects by altering the infectivity of the tissues into which it is transported through its capacity to perturb the electrostatic potential of the cellular membranes onto which it binds. On entry into a cell, squalamine would be expected to disturb the intracellular arrangement of membrane-associated proteins positioned by electrostatic forces, possibly including some of host or viral origin that is required for the viral replication cycle.”

The authors of the paper conclude with the proposal that squalamine should be tested as an anti-viral therapy in human clinical trials based on their recent findings and because it has already been shown to be safe during human clinical trials for treating cancer and retinal diseases.

But because the shark compound squalamine can only enter specific tissues such as blood vessels, capillaries and the liver, its usefulness toward fighting the influenza virus that attacks the lungs does not appear promising. However, what is promising is that the shark may prove to possess an as-of-yet-undiscovered lung-specific substance that can fight off an airway virus as well.

In a press release Dr. Zasloff hints at this with the statement, “I believe squalamine is one of a family of related compounds that protects sharks and some other ‘primitive’ ocean vertebrates, such as the sea lamprey, from viruses,” he says. “Squalamine appears to protect against viruses that attack the liver and blood tissues, and other similar compounds that we know exist in the shark likely protect against respiratory viral infections, and so on.”

An important point to all of this is that sharks and many other species that are at risk of becoming endangered may hold promise for us and our future survival. We need to think beyond a tree-hugging view of conservation and consider that perhaps instead, conservation may prove to be our preservation.

Source:
“Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential” Published online before print September 19, 2011, doi: 10.1073/pnas.1108558108 PNAS September 19, 2011
Press Release: http://explore.georgetown.edu/news/?ID=59193&PageTemplateID=295
Full article available free online at http://www.pnas.org/content/early/2011/09/13/1108558108.full.pdf+html?sid=b5bfd531-823a-49b9-912a-c6256c6a98b7

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