Researchers Develop New Strategy for Broad-Spectrum Antiviral Drugs

[Guest guest]

http://www.infectioncontroltoday.com/hotnews/new-strategy-for-antiviral-drugs.ht\

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Researchers Develop New Strategy for Broad-Spectrum Antiviral Drugs

11/24/2008

Bavituximab, an antiviral drug developed by UT Southwestern Medical Center

researchers, shows promise as a new strategy to fight viral diseases, including

potential bioterrorism agents.

In a study appearing in the December issue of Nature Medicine, groups of guinea

pigs infected with a virus similar to Lassa fever virus recovered from the fatal

disease when treated with bavituximab alone or in combination with a common

antiviral medication. Bavituximab treatment also cured mice infected with

cytomegalovirus, an opportunistic infection that afflicts transplant and AIDS

patients.

Dr. Philip Thorpe, professor of pharmacology at UT Southwestern and senior

author of the study, proposed that phosphatidylserine, a lipid molecule that is

normally positioned on the internal surface of a cell, flips to the outside of

the cell when the cell is infected by a virus. His laboratory developed

bavituximab, which binds to phosphatidylserine on the infected cells. Thorpe,

holder of the Serena S. Distinguished Chair in Cancer

Immunopharmacology, predicted that this interaction would muster the body's

immune cells to attack and destroy the infected cells before the virus has a

chance to replicate.

" When injected into the bloodstream, bavituximab circulates in the body until it

finds these inside-out lipids and then binds to them, " said Thorpe. " 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. "

In the study, half of the guinea pigs infected with a virus similar to the Lassa

fever virus were cured when bavituximab was administered alone. This is the

first report of a therapeutic treatment being effective against advanced

Lassa-like fever infections in animals. Lassa fever is an endemic disease in

portions of West Africa, where the Lassa virus is carried by rats. As a

hemorrhagic fever virus, Lassa is listed as a Category A bioterrorism agent –

the same class as the Ebola and Marburg viruses – by the Centers for Disease

Control and Prevention (CDC).

In a second experiment, researchers administered both bavituximab and the

anti-viral medication ribavirin. Ribavirin works by a different mechanism than

bavituximab; it stops virus replication in the cell. With this combination

therapy, 63 percent of guinea pigs survived.

Dr. Melina Soares, instructor of pharmacology at UT Southwestern and lead author

of the Nature Medicine study, said, " As viruses mutate, they become more

resistant to existing anti-viral drug therapies. Using bavituximab to attack a

lipid target could prove to be a new and effective strategy for treating virus

infections. "

Thorpe said that because phosphatidylserine on virus-infected cells is

host-derived and independent of the virus, drug-resistance should be less

problematic. " This approach reduces the ability of the virus to escape attack by

a drug, " he said. " Viruses often dodge drugs by mutating into a different form

that the drug is ineffective against. Host cells are a more immutable target. "

Bavituximab is currently in clinical trials to treat patients with hepatitis C.

The trials have shown that treatment is safe for patients, and researchers are

reporting a reduction in their blood-virus load.

UT Southwestern researchers have found that phosphatidylserine flipping occurs

in cells infected with influenza, the herpes simplex virus and viruses in the

families of the small pox and rabies viruses. Other researchers have shown that

this also occurs in HIV.

" It could very well be that this is a generic feature of enveloped viruses, "

Soares said. " It could lead to a new, broad spectrum anti-viral treatment. "

[Guest guest]

http://www.infectioncontroltoday.com/hotnews/new-strategy-for-antiviral-drugs.ht\

ml

Researchers Develop New Strategy for Broad-Spectrum Antiviral Drugs

11/24/2008

Bavituximab, an antiviral drug developed by UT Southwestern Medical Center

researchers, shows promise as a new strategy to fight viral diseases, including

potential bioterrorism agents.

In a study appearing in the December issue of Nature Medicine, groups of guinea

pigs infected with a virus similar to Lassa fever virus recovered from the fatal

disease when treated with bavituximab alone or in combination with a common

antiviral medication. Bavituximab treatment also cured mice infected with

cytomegalovirus, an opportunistic infection that afflicts transplant and AIDS

patients.

Dr. Philip Thorpe, professor of pharmacology at UT Southwestern and senior

author of the study, proposed that phosphatidylserine, a lipid molecule that is

normally positioned on the internal surface of a cell, flips to the outside of

the cell when the cell is infected by a virus. His laboratory developed

bavituximab, which binds to phosphatidylserine on the infected cells. Thorpe,

holder of the Serena S. Distinguished Chair in Cancer

Immunopharmacology, predicted that this interaction would muster the body's

immune cells to attack and destroy the infected cells before the virus has a

chance to replicate.

" When injected into the bloodstream, bavituximab circulates in the body until it

finds these inside-out lipids and then binds to them, " said Thorpe. " 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. "

In the study, half of the guinea pigs infected with a virus similar to the Lassa

fever virus were cured when bavituximab was administered alone. This is the

first report of a therapeutic treatment being effective against advanced

Lassa-like fever infections in animals. Lassa fever is an endemic disease in

portions of West Africa, where the Lassa virus is carried by rats. As a

hemorrhagic fever virus, Lassa is listed as a Category A bioterrorism agent –

the same class as the Ebola and Marburg viruses – by the Centers for Disease

Control and Prevention (CDC).

In a second experiment, researchers administered both bavituximab and the

anti-viral medication ribavirin. Ribavirin works by a different mechanism than

bavituximab; it stops virus replication in the cell. With this combination

therapy, 63 percent of guinea pigs survived.

Dr. Melina Soares, instructor of pharmacology at UT Southwestern and lead author

of the Nature Medicine study, said, " As viruses mutate, they become more

resistant to existing anti-viral drug therapies. Using bavituximab to attack a

lipid target could prove to be a new and effective strategy for treating virus

infections. "

Thorpe said that because phosphatidylserine on virus-infected cells is

host-derived and independent of the virus, drug-resistance should be less

problematic. " This approach reduces the ability of the virus to escape attack by

a drug, " he said. " Viruses often dodge drugs by mutating into a different form

that the drug is ineffective against. Host cells are a more immutable target. "

Bavituximab is currently in clinical trials to treat patients with hepatitis C.

The trials have shown that treatment is safe for patients, and researchers are

reporting a reduction in their blood-virus load.

UT Southwestern researchers have found that phosphatidylserine flipping occurs

in cells infected with influenza, the herpes simplex virus and viruses in the

families of the small pox and rabies viruses. Other researchers have shown that

this also occurs in HIV.

" It could very well be that this is a generic feature of enveloped viruses, "

Soares said. " It could lead to a new, broad spectrum anti-viral treatment. "