Scientists have known for some time that dogfish sharks, like the one pictured up top, naturally produce a broad-spectrum antibiotic called squalamine in their livers. Now, new research into the cellular function of squalamine reveals how it also confers a broad-spectrum antiviral benefit for the shark — one we humans could benefit from, as well.
Many sharks demonstrate a natural immunity to numerous forms of viral infection, even in the absence of a rapidly adapting immune system like ours. This observation got University of Pennsylvania geneticist Michael Zasloff thinking: what if researchers could identify the molecule (or molecules) responsible for conferring this antiviral characteristic?
"I was interested in sharks because of their seemingly primitive but effective immune system." Explains Zasloff. "No-one could explain why the shark was so hardy."
The research team figured that a good place to start looking would be the protein squalamine. Since its discovery in the livers of dogfish sharks 1993, squalamine has received quite a bit of attention for its antibacterial and antitumorigenic properties.
Some of the most recent research surrounding squalamine has revealed that it is also capable of displacing proteins commonly found anchored in cell membranes. (A cell's membrane is the barrier separating its insides from the outside environment, including other cells.) Zasloff hypothesized that squalamine's ability to displace membrane-anchored proteins could grant it antiviral properties, as well.
Zasloff and his colleagues explain their reasoning in the latest issue of Proceedings of the National Academy of Sciences:
Many viruses enter cells through engagement of [membrane-anchored proteins]...Displacement of key proteins anchored through electrostatic forces (of host or viral origin) from the cytoplasmic face of the plasma membrane might interfere with [viral] entry, protein synthesis, virion assembly, virion budding , or other steps in the viral replication cycle.
In other words, the researchers hypothesized that squalamine could interfere with a virus's ability to not only enter and infect healthy cells, but to replicate and propagate, as well.
And the researchers' results suggest that squalamine does exactly that. In tissue cultures and animal models, squalamine was shown to control — and, in some cases, cure — infections by hepatitis B, hepatitus D, yellow fever, dengue virus, Eastern equine encephalitus virus, and murine cytomegalovirus.
Zasloff's team says it has yet to optimize squalamine dosing in any of the animal models, and therefore does not know the maximum therapeutic benefit that can be achieved using squalamine, but their initial results are very encouraging.
The researchers also note that squalamine has already been studied in several phase II clinical trials, and has a known safety profile in humans. Given this, the researchers emphasize how important it is that the broad antiviral properties of squalamine be investigated further.
"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," explains Zasloff. He continues:
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. 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.