New technique could identify drugs that help fight broad range of viruses

Results of a new study demonstrate the feasibility of a novel strategy in drug discovery: screening large numbers of existing drugs — often already approved for other uses — to see which ones activate genes that boost natural immunity.

Using an automated, high-volume screening technique, researchers at Washington University School of Medicine in St. Louis have identified a cancer drug that enhances an important natural response to viral infection in human cells.

“Over many years of research, we have developed a good understanding of the human body’s own mechanisms to fight viruses,” says the study’s first author Dhara Patel, PhD, a postdoctoral research scholar at Washington University. “Instead of targeting the virus itself, which most current antiviral drugs do, we have designed a strategy to look for chemical compounds that will enhance this innate antiviral system.”

The results of the study, led by Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine, appear May 4 in PLoS ONE.

Of the 2,240 compounds the researchers tested, 64 showed increased activity in the cells’ interferon signaling pathway, an important player in the body’s response to viruses. The 64 compounds included many different classes of drugs treating conditions as diverse as depression, high blood pressure and ulcers. But the one that stood out is idarubicin, a cancer drug commonly prescribed to treat leukemia, lymphoma and breast cancer. Even at low doses, idarubicin significantly ramps up the interferon signaling system.

In treating cancer, idarubicin stops cells from dividing by blocking a protein that unwinds DNA. As long as DNA remains tightly packed, it can’t be copied. And if DNA can’t be copied, a cell can’t divide. Interestingly, though, the researchers showed that idarubicin’s antiviral effects are totally unrelated to what makes it a good cancer drug.

Patel