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Researchers discover new mechanism of drug that alters genetic makeup of viruses

Researchers at Penn State have discovered a new mechanism for an existing antiviral drug that could permit the design and production of a new class of antiviral agents to treat RNA viruses. Such viruses, a family that includes poliovirus and hepatitis C, use RNA as both their core genetic material and also to direct protein synthesis.

A paper published in the December 2000 issue of Nature Medicine, by a team led by Craig Cameron, assistant professor of biochemistry and molecular biology at Penn State, reveals that ribavirin, a synthetic compound that inhibits RNA viruses by working at the cellular level, also possesses an ability to alter the structure of the viruses at the genetic level. Researchers used poliovirus as the experimental model for their work.

"Our results indicate the antiviral effects of ribavirin come from its direct incorporation into the viral RNA," Cameron said. "When that happens, it changes the behavior of the base pairs of the RNA and the virus no longer produces faithful copies of itself. In that manner, ribavirin effectively shifts the internal balance of the virus and the virus suffers from a genetic meltdown."

While most organisms use DNA as their genetic material and RNA to direct protein synthesis, RNA viruses use RNA for both functions. When an RNA virus infects a cell, it directs the synthesis of proteins used to make copies of the original RNA and then uses those copies to build the chromosomes of the virus. Many RNA viruses can be stopped by intervention from the immune system or with the help of vaccinations. Others adapt, developing their own "quasispecies" so rapidly that neither the immune system nor vaccinations provide relief.

In general, RNA's instabilitywhen compared to DNAmeans it works well as a virus because it changes form, or mutates, often enough to prevent the immune system from providing effective antiviral activity. With ribavirin acting at the genetic level, researchers have discovere
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Contact: Steve Sampsell
sws102@psu.edu
814-865-1390
Penn State
4-Dec-2000


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