Shark-Derived Drug May Treat Viruses - Squalamine Has New Antiviral Properties, Researchers Say

[Guest guest]

http://www.webmd.com/news/20110919/shark-derived-drug-may-treat-viruses

Shark-Derived Drug May Treat Viruses

Squalamine Has New Antiviral Properties, Researchers Say

By Salynn Boyles

WebMD Health News

Reviewed by J. , MD

Sept. 19, 2011 -- A unique compound originally isolated from sharks could prove

to be a promising treatment for hepatitis B and C and other viral diseases,

researchers say.

Known as squalamine, the drug has not yet been tested as an antiviral agent in

humans, but it has been given to hundreds of people enrolled in clinical trials

designed to test its usefulness for other conditions.

Researchers say they hope to begin human trials to test the compound’s

antiviral activity within the next year.

town University Medical Center researcher Zasloff, MD, PhD, and

colleagues first discovered squalamine almost two decades ago while studying

sharks in hopes of finding new, naturally occurring antibiotic agents.

He tells WebMD that he chose sharks because they have very primitive, but highly

effective, immune systems.

His more recent research led to the discovery that the shark-derived compound

works in a completely new way that could make it an effective antiviral drug, he

says.

“Sharks ought to be riddled with viruses because they have such primitive

immune systems, but they aren’t,†Zasloff says. “Other vertebrates are

vulnerable to viruses, but there are no known shark viruses.â€

To test the theory that squalamine had antiviral properties, he sent samples of

the compound -- now synthesized in the lab without shark tissue -- to viral

researchers across the country.

Laboratory and animal studies confirmed that it had “unambiguous†activity

against viruses that attack cells in the liver and blood, including those that

cause hepatitis B, C, and D, yellow fever, and dengue fever, Zasloff says.

The study appears online in the journal PNAS Early Edition.

“This agent works in a completely novel way,†he says. “There is no known

compound that does what squalamine is capable of doing.â€

Squalamine Changes Cell’s Electrical Charge

Instead of targeting the virus directly, squalamine helps protect the cells that

line the liver and blood vessels from infection, Zasloff says.

It does this by changing the electrical balance within the cells, eliminating

certain positively charged proteins that are bound to the negatively charged

surface of the cells’ inner linings.

This includes proteins that are critical to viral replication. Changing the

proteins disrupts the life cycle of the virus.

Zasloff says squalamine acts fast to stop viral replication by clearing the body

of the invading virus within hours.

He adds that because it works by making the host tissue less receptive to

infection instead of directly targeting the virus, viral resistance may not be

an issue.

Infectious disease specialist Bruce Hirsch, MD, calls the research intriguing,

but he says it is too soon to say if the compound will prove to be a useful

antiviral agent in humans.

Hirsch is an attending physician at North Shore University Hospital in

Manhasset, N.Y.

“This approach might be especially useful for viral diseases characterized by

ongoing viral replication like HIV and Hepatitis C,” he says. “A strategy like

this could prove very interesting.”

But he questions whether a treatment that changes the electrical balance of

cells would prove safe for long-term use.

Zasloff says the drug has a proven safety profile and there were few side

effects reported in the earlier clinical trials.

“Electrical balance is a vital aspect of cell biology,” Hirsch says. “We are

programmed at a basic level to maintain a gradient of electric charge over our

cell membranes. I am surprised that there wasn’t toxicity with this.”

The research was funded with grants from the National Science Foundation, the

National Institute for Allergy and Infectious Diseases, and other public

sources.

Zasloff, who holds the patent on the technology used in the study, says he is

seeking private funding to study squalamine in humans.

[Guest guest]

http://www.webmd.com/news/20110919/shark-derived-drug-may-treat-viruses

Shark-Derived Drug May Treat Viruses

Squalamine Has New Antiviral Properties, Researchers Say

By Salynn Boyles

WebMD Health News

Reviewed by J. , MD

Sept. 19, 2011 -- A unique compound originally isolated from sharks could prove

to be a promising treatment for hepatitis B and C and other viral diseases,

researchers say.

Known as squalamine, the drug has not yet been tested as an antiviral agent in

humans, but it has been given to hundreds of people enrolled in clinical trials

designed to test its usefulness for other conditions.

Researchers say they hope to begin human trials to test the compound’s

antiviral activity within the next year.

town University Medical Center researcher Zasloff, MD, PhD, and

colleagues first discovered squalamine almost two decades ago while studying

sharks in hopes of finding new, naturally occurring antibiotic agents.

He tells WebMD that he chose sharks because they have very primitive, but highly

effective, immune systems.

His more recent research led to the discovery that the shark-derived compound

works in a completely new way that could make it an effective antiviral drug, he

says.

“Sharks ought to be riddled with viruses because they have such primitive

immune systems, but they aren’t,†Zasloff says. “Other vertebrates are

vulnerable to viruses, but there are no known shark viruses.â€

To test the theory that squalamine had antiviral properties, he sent samples of

the compound -- now synthesized in the lab without shark tissue -- to viral

researchers across the country.

Laboratory and animal studies confirmed that it had “unambiguous†activity

against viruses that attack cells in the liver and blood, including those that

cause hepatitis B, C, and D, yellow fever, and dengue fever, Zasloff says.

The study appears online in the journal PNAS Early Edition.

“This agent works in a completely novel way,†he says. “There is no known

compound that does what squalamine is capable of doing.â€

Squalamine Changes Cell’s Electrical Charge

Instead of targeting the virus directly, squalamine helps protect the cells that

line the liver and blood vessels from infection, Zasloff says.

It does this by changing the electrical balance within the cells, eliminating

certain positively charged proteins that are bound to the negatively charged

surface of the cells’ inner linings.

This includes proteins that are critical to viral replication. Changing the

proteins disrupts the life cycle of the virus.

Zasloff says squalamine acts fast to stop viral replication by clearing the body

of the invading virus within hours.

He adds that because it works by making the host tissue less receptive to

infection instead of directly targeting the virus, viral resistance may not be

an issue.

Infectious disease specialist Bruce Hirsch, MD, calls the research intriguing,

but he says it is too soon to say if the compound will prove to be a useful

antiviral agent in humans.

Hirsch is an attending physician at North Shore University Hospital in

Manhasset, N.Y.

“This approach might be especially useful for viral diseases characterized by

ongoing viral replication like HIV and Hepatitis C,” he says. “A strategy like

this could prove very interesting.”

But he questions whether a treatment that changes the electrical balance of

cells would prove safe for long-term use.

Zasloff says the drug has a proven safety profile and there were few side

effects reported in the earlier clinical trials.

“Electrical balance is a vital aspect of cell biology,” Hirsch says. “We are

programmed at a basic level to maintain a gradient of electric charge over our

cell membranes. I am surprised that there wasn’t toxicity with this.”

The research was funded with grants from the National Science Foundation, the

National Institute for Allergy and Infectious Diseases, and other public

sources.

Zasloff, who holds the patent on the technology used in the study, says he is

seeking private funding to study squalamine in humans.