September 29, 2011
Sharks’ Virus Killer Could Cure Humans, Study Suggests
“Remarkable property” already effective against six types of viruses. Sharks aren’t just tough on the outside—a substance in their bodies can stop viruses in their tracks, a new study says.
A cholesterol-like compound found in dogfish sharks’ tissue has been shown to combat several viruses that cause hard-to-treat human diseases, such as dengue fever and hepatitis, a new study says. Called squalamine, the compound is already in human clinical trials for cancer and eye disorders, and several hundred people have been exposed without major side effects.
The new study revealed that squalamine can also disrupt a virus’s life cycle and prevent it from replicating in both tissue cultures and live animals. Though there are plenty of drugs to treat bacterial infections, there are few pharmaceuticals that are effective against viruses. Current antiviral drugs are highly specific—each targeting just one strain of a virus—but strains can easily mutate and become resistant to the medication.
“It’s a whole new approach to treatment of viral disease,” said study leader Michael Zasloff, of the Georgetown University Medical Center. “It’s very possible we could cure several diseases we [now] treat as chronic infections.”
“Eureka Moment” for Shark-based Antiviral Drug
Zasloff discovered squalamine in 1993 while searching for antibacterial agents in sharks, which are immune to some diseases, including all viruses. He found that squalamine—which “looked like nothing else that had ever been described or discovered”—inhibits the growth of blood vessels, suggesting the molecule could potentially stop cancer cells from multiplying. Human research eventually led to Zasloff’s “eureka moment,” when he realized squalamine can also disable viruses, he said. “I could see [how it works against viruses] almost as if it were a moving picture,” he recalled.
Squalamine is a positively charged molecule, so when it enters a cell, the molecule immediately sticks “like Velcro” to the cell’s inner membranes, which have negative charges, Zasloff said. By doing so, squalamine “pops off” any positively charged proteins that were attached to the cell membrane—an action that does no harm to the cell, Zasloff noted. When a virus invades a cell, it expects those proteins to be present on the cell membrane. Without them, the virus can’t reproduce. “There is no other compound known to science that does this—this is a remarkable property,” Zasloff said. It’s also one that has apparently served sharks well for hundreds of millions of years—and possibly explains the creatures’ evolutionary success. The shark’s “antiviral defenses have been extraordinary,” Zasloff said. “It has adapted a very remarkable immune system and stayed with it.”
Squalamine Effective Against Human Viruses
In the study, squalamine thwarted infection of the dengue fever virus in human blood vessel cells and of hepatitis B and D in human liver cells—and with little harm to sharks. Shark tissue is no longer required to produce squalamine, which has been synthesized in the laboratory since 1995.
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, published this week in the journal Proceedings of the National Academy of Sciences.
Current squalamine compounds can access only cells that have …
See the source (http://tinyurl.com/3ft4rgt) for the full story.
[The PNAS study is accessible from http://tinyurl.com/3swqcpt. ADS-Mod.]
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