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Potent Drugs for Genital Herpes on Horizon

Resistant viral strains may have met their match

TUESDAY, April 2, 2002 (HealthDayNews) -- Two new compounds might someday offer relief to the millions of Americans with genital herpes.

Researchers working in the United States and Germany have identified two potential drugs – the first possible additions to the anti-herpes arsenal since acyclovir was approved in 1977.

Like acyclovir, the new compounds interfere with the replication of herpes DNA, but the new compounds target an earlier step of the process.

At least 47 million Americans are infected with HSV type 2 (HSV-2), which is more commonly associated with genital herpes. Meanwhile, the American Social Health Association estimates that 50 percent to 80 percent of the adult U.S. population has oral herpes, which is usually caused by HSV type 1 (HSV-1).

An expert in herpes therapy says the new findings, which appear in the current issue of Nature Medicine, could help patients struggling with herpes strains that are resistant to acyclovir.

Researchers at Ridgefield, Conn.-based Boehringer Ingelheim Pharmaceuticals identified the first compound, called BILS 179 BS.

Study author James J. Crute, who now leads a gene expression research team at Aurora Biosciences Corp. in San Diego, says the compound was more potent than acyclovir against skin and vaginal lesions in mice with HSV-1 and HSV-2. The compound can be given orally.

Crute describes three basic steps that take place when the herpes virus replicates its DNA. First, pieces of RNA "primers" need to kick-start the replication process. This triggers the second step, when the DNA's coiled ladder-like structure unwinds, halves lengthwise, doubles each half, and puts the halves back together to form two identical but separate double helices. Finally, DNA "polymerase" finishes the replication.

While acyclovir targets the DNA polymerase, BILS 179 BS targets the first step, Crute says.

"It's kind of like throwing a monkey wrench into your car," Crute says. "Your engine will just kind of stop and seize up. The compound actually works by stalling the enzyme on DNA, and preventing replication."

However, Crute says the safety of the drug in humans is still untested.

"There's no indication that there's any toxicity associated with [BILS 179 BS]," Crute says. "But until you have human safety data, you don't know if it's safer than acyclovir."

Crute says the new drug works both in initial infections, and when herpes comes out of its latent phase and flares up. In the study, the compound appeared effective against multiple strains of HSV that have developed resistance to acyclovir.

In the second study, researchers at Bayer AG Pharma Research in Germany report that a similar compound called BAY 57-1293 reduced the healing time of herpes lesions in mice with HSV.

Priscilla A. Schaffer, a professor of medicine at Harvard Medical School in Boston, says the major advantage of this new class of compounds is the potential to treat resistant strains of HSV.

"Right now, the acyclovir-related compounds have been the gold standard, and they are very, very good," she says. "They don't have many side effects, they're very potent and they've had a huge positive effect on people who suffer from herpes simplex virus."

However, since acyclovir has become available over the counter, she says, misuse of the drug has encouraged the development of mutated, acyclovir-resistant strains of HSV.

"The major contribution of this new class of compounds is to be able to treat existing drug-resistant viruses," says Schaffer.

Crute notes that while HSV is rarely fatal, members of the herpes family can be dangerous for certain vulnerable populations, including recent organ transplant recipients, people with HIV and fetuses.

He adds that the findings prove that compounds can target the same step in other herpes viruses, such as cytomegalovirus.

If the compounds are well tolerated in humans, Schaffer suspects that once they hit the market and more information is gathered about their effect, they may become the new gold standard for treating HSV.

However, she stresses that neither the compounds nor acyclovir have any effect on the latent phase of HSV, when the virus lies dormant in the body. Schaffer says new therapies against this phase or a vaccine are still badly needed.

What to Do: These fact sheets from the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases provide information primarily about genital herpes, while NetDoctor.Co.UK publishes information on cold sores.

SOURCES: James J. Crute, Ph.D., group leader, Gene Expression, Aurora Biosciences Corporation, San Diego, Calif.; Priscilla A. Schaffer, Ph.D., professor, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston; April 2002 Nature Medicine
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