Squalamine, a compound found in sharks, has great potential for treating human viruses and is known to be safe for humans to use, scientists from Georgetown University Medical Center wrote in the Proceedings of the National Academy of Sciences. Squalamine has been used in clinical trials for eye disorders and the treatment of cancer. Its safety profile is well established, meaning it could rapidly be tested as a new class of medications for the treatment of various viruses, such as hepatitis, dengue or yellow fever.
Squalamine, molecular formula C34 H65 N3 O5 S, has been demonstrated in laboratory and animal experiments to have strong antiviral activity against several human pathogens. Some of these human pathogens are not effectively treated with current medications.
Study leader, Michael Zasloff, M.D., Ph.D., said:
“To realize that squalamine potentially has broad antiviral properties is immensely exciting, especially since we already know so much from ongoing studies about its behavior in people.”
Apart from the potential uncovered by Zasloff and team, they may also have solved a longstanding enigma regarding shark health. Sharks have an extremely primitive immune system but are good at fighting off viruses.
Zasloff said:
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.”
Squalamine was discovered by Zasloff 18 years ago when he worked at the University of Pennsylvania and was seeking out new antibacterial agents.
Zasloff said:
“I was interested in sharks because of their seemingly primitive but effective immune system. No one could explain why the shark was so hardy.”
After playing around with the compound, he found that it could well treat other disorders due to various properties in it that he had detected.
Zasloff discovered that squalamine blocked the growth of blood vessels that feed tumors, it also inhibits the rapid growth of blood cells in certain retinal diseases, such as diabetic retinopathy and macular degeneration. Some clinical trials in these areas are still underway.
In order to obtain squalamine, scientists do not need to catch sharks, they have been able to synthesize it in the lab since 1995.
Zasloff has always been fascinated by how squalamine, a natural cholesterol-like molecule, works as an immune agent in sharks. He knew the molecule has a net positive electrical charge. He later found out that when squalamine enters cells – it can only access certain kinds, such as those in capillaries, in the liver and blood vessels – it releases positively-charged proteins that are bound to the negatively-charged surface of the cell’s inner membrane. Viruses use some of these displaced proteins to replicate – if they are not available, the life cycle of the virus is disrupted.
Zasloff said:
“To me, the key to squalamine is that once in the body it times its action to match the life cycle of most viruses. Most viruses take hours to complete their life cycle, the same time period that squalamine renders tissues and organs viral resistant after administration. In addition, it acts fast to stop viral replication, clearing the body of these predators within hours.
Furthermore, because squalamine acts by making the host’s tissues less receptive for infection, rather than by targeting a specific viral protein, the emergence of viral resistance would not be anticipated.”
In order to further demonstrate squalamine’s potency, Zazloff sent the compound to various laboratories around the USA.
Tissue culture studies found that squalamine inhibits human blood vessel cell infection by the dengue virus as well as human liver cells infected with hepatitis viruses.
It was also found to control yellow fever infections, as well as suppressing Eastern equine encephalitis virus, and murine cytomegalovirus – in some cases the animals were completely cured.
Zasloff said:
“We have not yet optimized squalamine dosing in any of the animal models we have studied and as yet we do not know the maximum protective or therapeutic benefit that can be achieved in these systems. But we are sufficiently convinced of the promise of squalamine as an antiviral agent that we intend to take this compound into humans.
It is clearly a promising drug, and is unlike, in its mechanism of action and chemical structure, any other substance currently being investigated to treat viral infections.”
Written by Christian Nordqvist