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Shark-Derived Drug May Treat Viruses

A unique compound originally isolated from sharks could prove to be a promising treatment for hepatitis B and C and other viral conditions, researchers say.

Sept. 19, 2011 -- A unique compound originally isolated from sharks could prove to be a promising treatment for hepatitis B and C and other viral diseases, researchers say.

Known as squalamine, the drug has not yet been tested as an antiviral agent in humans, but it has been given to hundreds of people enrolled in clinical trials designed to test its usefulness for other conditions.

Researchers say they hope to begin human trials to test the compound’s antiviral activity within the next year.

Sharks Don’t Get Viruses

Georgetown University Medical Center researcher Michael Zasloff, MD, PhD, and colleagues first discovered squalamine almost two decades ago while studying sharks in hopes of finding new, naturally occurring antibiotic agents.

He tells WebMD that he chose sharks because they have very primitive, but highly effective, immune systems.

His more recent research led to the discovery that the shark-derived compound works in a completely new way that could make it an effective antiviral drug, he says.

“Sharks ought to be riddled with viruses because they have such primitive immune systems, but they aren’t,” Zasloff says. “Other vertebrates are vulnerable to viruses, but there are no known shark viruses.”

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.

Laboratory and animal studies confirmed that it 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, Zasloff says.

The study appears online in the journal PNAS Early Edition.

“This agent works in a completely novel way,” he says. “There is no known compound that does what squalamine is capable of doing.”

Squalamine Changes Cell’s Electrical Charge

Instead of targeting the virus directly, squalamine helps protect the cells that line the liver and blood vessels from infection, Zasloff says.

It does this by changing the electrical balance within the cells, eliminating certain positively charged proteins that are bound to the negatively charged surface of the cells’ inner linings.

This includes proteins that are critical to viral replication. Changing the proteins disrupts the life cycle of the virus.

Zasloff says squalamine acts fast to stop viral replication by clearing the body of the invading virus within hours.

He adds that because it works by making the host tissue less receptive to infection instead of directly targeting the virus, viral resistance may not be an issue.

Infectious disease specialist Bruce Hirsch, MD, calls the research intriguing, but he says it is too soon to say if the compound will prove to be a useful antiviral agent in humans.

Hirsch is an attending physician at North Shore University Hospital in Manhasset, N.Y.

“This approach might be especially useful for viral diseases characterized by ongoing viral replication like HIV and Hepatitis C,” he says. “A strategy like this could prove very interesting.”

But he questions whether a treatment that changes the electrical balance of cells would prove safe for long-term use.

Zasloff says the drug has a proven safety profile and there were few side effects reported in the earlier clinical trials.

“Electrical balance is a vital aspect of cell biology,” Hirsch says. “We are programmed at a basic level to maintain a gradient of electric charge over our cell membranes. I am surprised that there wasn’t toxicity with this.”

The research was funded with grants from the National Science Foundation, the National Institute for Allergy and Infectious Diseases, and other public sources.

Zasloff, who holds the patent on the technology used in the study, says he is seeking private funding to study squalamine in humans.

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