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Novel antiviral drug concept targets number of human viruses

protein would kill the cell," says Priscilla A. Schaffer, Ph.D., chair of microbiology and senior author on the study. "We've discovered that's not true -- by inhibiting a specific type of cellular enzyme, we've been able to completely block all viral activity without damaging the cells."

The pivotal enzymes are called cyclin-dependent kinases, or cdks. Cells use cdks, along with other proteins, to drive and coordinate cell division. Many viruses, too, rely on cellular cdks for their replication.

The Penn scientists were aware that Laurent Meijer, Ph.D., and his colleagues at the Centre National de la Recherche Scientifique in Roscoff, France, had developed and characterized a variety of cdk-specific inhibitors. With Meijer's assistance, they introduced his inhibitors into HSV-infected cells to test their antiviral theory. What they found was that viral replication ceased while the cells continued to be healthy.

Since the cells depend on cdks for their division but not for many other essential functions, they simply stop dividing in the presence of the drugs. But HSV depends absolutely on cdks for at least three steps in its life cycle, as is likely the case for other viruses, making it vulnerable to cdk inhibitors in multiple ways.

Additionally, the focused reliance of the viruses on cdks, combined with the fact that cdks are cellular, not viral, proteins, strongly suggests that the viruses will have a vanishingly small chance of mutating to develop resistance to cdk inhibitors.

Among the strains of virus completely inactivated by the cdk inhibitors in the Penn experiments were HSV-1 and HSV-2, which chronically infect 80 percent and 20 percent of the world's population respectively and are responsible for painful oral, and genital lesions, themselves a risk factor for sexually transmitted diseases and other health problems. HSV infections can also result in blindness and occasionally in fatal encephalitis.

Thomas Albrecht, Ph.
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Contact: Franklin Hoke
frank.hoke@nasw.org
215-662-2560
University of Pennsylvania School of Medicine
20-Apr-2000


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