An antibiotic found in liver of sharks 'could revolutionise human medicine'By Ted Thornhill
Last updated at 1:55 AM on 20th September 2011
The compound, found in the liver of the predator, could be used as a new type of drug to treat a broad spectrum of diseases from dengue and yellow fever to hepatitis B, C and D.
The antibiotic, squalamine, is already known to be safe for use in humans as an antiviral agent.
They found that in both lab and animal experiments squalamine produced antiviral activity against the human pathogens found in the diseases such as some forms of hepatitis which cannot currently be treated.
Along with offering medical advances this discovery may solve the mystery of how sharks with primitive immune systems can so effectively fight viruses that plague all living creatures.
Dr Zasloff said: ‘I believe squalamine is one of a family of related compounds that protects sharks and some other “primitive” ocean vertebrates, such as the sea lamprey, from viruses.
‘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, and so on.
‘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.’
Dr Zasloff discovered squalamine in 1993 and it has already been used in clinical trials to treat cancer and several eye disorders.
‘I was interested in sharks because of their seemingly primitive but effective immune system. No one could explain why the shark was so hardy,’ he said.
Since 1995 it has been synthesised in the laboratory rather than taking any natural shark tissue.
Dr Zasloff remained interested in how the natural cholesterol type molecule, which has a net positive electrical charge, acted as an immune agent in sharks.
When it enters cells, and it can only access certain cells including those in blood vessels, capillaries and the liver, squalamine ‘kicks off’ positively-charged proteins that are bound to the negatively charged surface of the cells inner membrane.
Some of these displaced proteins are used by viruses to replicate and without the protein a virus's life cycle is disrupted, the microbe is rendered inert and the cell containing it is destroyed.
This means that squalamine seems to be designed to fight certain viral infections, Dr Zasloff claimed.
He 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 tissue culture studies squalamine was shown to inhibit the infection of human blood vessel cells by the dengue virus and human liver cells infected with hepatitis B and D, which can cause liver failure and cancer.
In animal studies, scientists from across the USA discovered that squalamine controlled infections of yellow fever, Eastern equine encephalitis virus, and murine cytomegalovirus, and in some cases cured the animals.
The study was published in the Proceedings of the National Academy of Sciences Early Edition online yesterday.