Antivirals from shark cartilage compound squalamine

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.

Georgetown University Medical Center researcher Michael Zasloff, and colleagues first discovered squalamine almost two decades ago while studying sharks in hopes of finding new, naturally occurring antibiotic agents. He explained 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 said. “Sharks ought to be riddled with viruses because they have such primitive immune systems, but they aren’t,” Zasloff said. “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 said.

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.” Instead of targeting the virus directly, squalamine helps protect the cells that line the liver and blood vessels from infection, Zasloff explained. 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 said squalamine acts fast to stop viral replication by clearing the body of the invading virus within hours. He added 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.

Zasloff and colleagues also discovered that squalamine inhibited yellow fever, eastern equine encephalitis virus, and murine cytomegalovirus in lab animals—in some cases curing the subjects, according to the study.

Infectious disease specialist Bruce Hirsch, 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. “This approach might be especially useful for viral diseases characterized by ongoing viral replication like HIV and Hepatitis C,” he said. “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.

“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 results “sounds promising” as antiviral drugs, said Todd Rider, a senior staff scientist at the Massachusetts Institute of Technology's Lincoln Laboratory and Division of Comparative Medicine. “So far the researchers appear to have shown that squalamine is active against six viruses, although they also found that it does have some toxicity and other side effects in certain cell types at doses roughly comparable to those that were required for antiviral efficacy,” Rider said. “It will be interesting to see what additional viruses squalamine is or is not effective against, and whether the antiviral efficacy can be achieved without toxicity in any type of tissue.”

Shark tissue is no longer required to produce squalamine, which has been synthesized in the laboratory since 1995. Sharks have been hiding squalamine in their bodies for 700 million years, Zasloff added.  “Now it's a gift to us.” The research was funded with grants from the National Science Foundation, the National Institute for Allergy and Infectious Diseases, and other public sources.

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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