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Shark-Produced Steroid Shows Promise for Fighting Human Viruses | 80beats

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The spiny dogfish

What’s the News: Researchers found that squalamine, a steroid present in the bodies of the dogfish shark, has a protective effect against several human viruses, all of which are difficult or impossible to cure with existing drugs. The chemical has so far been shown to be relatively safe in humans and can be synthesized, suggesting it could have promise as an antiviral drug in humans.

How the Heck: 

  • In one test, scientists injected hamsters with the yellow fever virus, which kills 30,000 people per year. Half of the hamsters got squalamine and half got nothing (a placebo). By day 11, all of the untreated hamsters were dead, but 60 percent of the squalamine-treated rodents survived.
  • Next, researchers bathed lab-grown human endothelial cells—the type that line blood vessels—in varying concentrations of squalamine before introducing dengue virus. At the highest concentration of the chemical, none of the human cells became infected, nor suffered any visible ill effects from the squalamine.
  • Researchers also tested squalamine’s ability to prevent replication of the hepatitis B and D viruses in cultured human liver cells. In cells treated with squalamine, viral replication was reduced 10-fold.

What’s the Context: 

  • Squalamine has antibiotic, fungicidal, and anti-protozoan properties. It kills a wide variety of pathogens and one study found it could be used to treat multidrug-resistant bacteria. Researchers are also investigating its ability to treat cancer and fight macular degeneration.
  • A positively charged steroid similar in structure to cholesterol, squalamine binds to cell surfaces and deactivates the membrane’s negative charge before entering the cell. Researchers suspect this activity may interfere with viruses’ ability to bind to and replicate within their host.
  • The chemical was first found in the spiny dogfish, or Squalus acanthias, in 1993 and named for it. Dogfish and other sharks show a remarkable resistance to viruses and other pathogens that scientists think may be due in part to squalamine.
Not So Fast: 
  • As with any research at this stage, results from tests in animals and lab-grown cells may not translate as expected to humans, and many steps remain before using squalamine as a antiviral drug in people.
  • Squalamine only binds to certain cell types, such as liver and endothelial cells. This limits the number of bugs it might be able to fight. It also has a relatively short half-life of one to five hours in humans, potentially limiting its usefulness in certain conditions.
  • Researchers don’t know the exact mechanism by which squalamine inhibits or fights viruses, and it may turn out to cause unforeseen limitations or side effects at certain dosages, although it has generally been well-tolerated in trials to date.
  • Squalamine doesn’t cross the blood-brain barrier and thus is unlikely to treat viruses that affect the brain. Curiously, the researchers did test the chemical’s impact on hamsters infected with Eastern equine encephalitis virus, a pathogen that attacks the central nervous system of horses and people. Although hamsters given squalamine lived slightly longer on average than their untreated brethren, all of them still died within two weeks.

The Future Holds:

  • Squalamine shows promise as a potential antiviral drug in humans, but many questions must be answered and steps taken before that can happen. In the near term, if current tests pan out, it will probably first be used to treat certain cancers or macular degeneration—which would in itself be impressive.
  • If squalamine is to be used widely in the future, it’s important that it is synthesized and doesn’t come from the sharks themselves. (Squalamine used in the study was synthesized, as pointed out in the comments.) Once one of the world’s most abundant sharks, the dogfish is now listed by the IUCN Red List of Threatened Species as vulnerable, one step above “endangered.” And yet very little is being done to prevent its further decline.

Reference: Michael Zasloff et al. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1108558108

Image: OCVA / Flickr


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