Inside-out cells offer target for antiviral drugs

CHICAGO Sun Nov 23, 2008 1:00pm EST

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CHICAGO Nov 23 (Reuters) - An experimental drug cured guinea pigs infected with a fatal hemorrhagic fever virus, raising hope for its use in a broad range of viral diseases including influenza, hepatitis C, HIV, Ebola and others, U.S. researchers said on Sunday.

"This is a whole new strategy for making antiviral drugs," said Dr. Philip Thorpe, professor of pharmacology at the University of Texas Southwestern Medical Center at Dallas, whose research appears in the journal Nature Medicine.

Instead of attacking the virus directly, bavituximab, made by Peregrine Pharmaceuticals Inc (PPHM.O), takes advantage of a defense mechanism used by the virus to hide from the immune system, Thorpe said.

When cells are under attack by a virus, this stress causes a fat molecule called phosphatidylserine, which normally lines the inside of the cell, to flip to the outside. "It's like wearing your clothes inside out," Thorpe, a scientific adviser to Peregrine, said in a telephone interview.

Bavituximab, a genetically engineered antibody, seeks out and attaches itself to these turncoat cells, flagging them for the immune system, which can then mount an attack,

"When injected into the bloodstream, bavituximab circulates in the body until it finds these inside-out lipids and then binds to them," Thorpe said in a statement.

"In the case of virus infection, the binding raises a red flag to the body's immune system, forcing the deployment of defensive white blood cells to attack the infected cells."

Thorpe said conventional antiviral drugs try to exploit some property of the virus, but these drugs are often quickly defeated as the virus mutates.

By targeting an aspect of infected cells in the host, he thinks bavituximab is less likely to lose effectiveness, which commonly happens when a virus mutates.

In the study, Thorpe and his colleagues tested the compound on guinea pigs in an advanced stage of infection with a form of the Lassa fever virus, a disease that affects parts of West Africa.

Half of the animals treated with the drug alone were cured. When the researchers tested it in combination with the antiviral drug ribavirin, a drug that keeps a virus from replicating, 63 percent of the guinea pigs lived.

Thorpe said the findings suggest the drug might be effective on other types of hemorrhagic viruses, such as Ebola and Marburg. But this lipid flipping also occurs in cells infected with many other viral infections, including influenza, smallpox and rabies.

Peregrine is conducting early phase clinical trials of the drug in people with hepatitis C and human immunodeficiency virus, or HIV, which causes AIDS. And it has more advanced trials under way in cancer.

"We think it has tremendous potential," Steven King, president and chief executive of Peregrine, said in a telephone interview. Peregrine funded the research along with the National Institutes of Health. (Editing by Will Dunham and Todd Eastham)

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