An anti-viral drug developed at UT Southwestern, called bavituximab, has shown promise as a new strategy to fight viral diseases, including potential bio-terrorism agents.
The researchers have shown that bavituximab can cure lethal virus infections in animal disease models.
In the study, it was found that groups of guinea pigs infected with a virus similar to Lassa fever virus successfully recovered from the fatal disease after being treated with bavituximab alone or in combination with a common anti-viral medication.
Treatment with bavituximab also cured mice infected with cytomegalovirus, an opportunistic infection that afflicts transplant and AIDS patients.
According to Dr. Philip Thorpe, professor of pharmacology at UT Southwestern and senior author of the study, 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 predicted that such interaction would congregate the body's immune cells in order to attack and destroy the infected cells before allowing the virus to replicate.
"When injected into the bloodstream, bavituximab circulates in the body until it finds these inside-out lipids and then binds to them. 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," Nature magazine quoted Thorpe as saying.
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.
In another experiment, researchers administered both bavituximab and the anti-viral medication ribavirin, which adopts a different mechanism than bavituximab: it stops virus replication in the cell. 63 percent of guinea pigs survived with the combination therapy.
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 claimed that drug-resistance should be less problematic as phosphatidylserine on virus-infected cells is host-derived and independent of the virus.
"This approach reduces the ability of the virus to escape attack by a drug. Viruses often dodge drugs by mutating into a different form that the drug is ineffective against. Host cells are a more immutable target," he said.
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.
The 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. It could lead to a new, broad spectrum anti-viral treatment," said Soares.
The study is appearing in the upcoming issue of Nature Medicine.