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Results of a new study demonstrate the feasibility of a novelstrategy in drug discovery: screening large numbers of existingdrugs - often already approved for other uses - to see which onesactivate genes that boost natural immunity. Using an automated, high-volume screening technique, researchers atWashington University School of Medicine in St. Louis haveidentified a cancer drug that enhances an important natural response to viralinfection in human cells. "Over many years of research, we have developed a goodunderstanding of the human body's own mechanisms to fight viruses,"says the study's first author Dhara Patel, PhD, a postdoctoralresearch scholar at Washington University. "Instead of targetingthe virus itself, which most current antiviral drugs do, we havedesigned a strategy to look for chemical compounds that willenhance this innate antiviral system." The results of the study, led by Michael J. Holtzman, MD, the Selmaand Herman Seldin Professor of Medicine, appear in PLoS ONE. Of the 2,240 compounds the researchers tested, 64 showed increasedactivity in the cells' interferon signaling pathway, an importantplayer in the body's response to viruses. The 64 compounds includedmany different classes of drugs treating conditions as diverse as depression , high blood pressure and ulcers. But the one that stood out is idarubicin, a cancerdrug commonly prescribed to treat leukemia , lymphoma and breast cancer. Even at low doses, idarubicin significantly ramps up theinterferon signaling system. In treating cancer, idarubicin stops cells from dividing byblocking a protein that unwinds DNA. As long as DNA remains tightlypacked, it can't be copied. And if DNA can't be copied, a cellcan't divide. Interestingly, though, the researchers showed thatidarubicin's antiviral effects are totally unrelated to what makesit a good cancer drug. "We tested other cancer drugs that work the same way as idarubicinbut have very different structures," Patel says. "Although they actthe same way that idarubicin does in cancer cells, they had noeffect on the interferon system." Like many cancer drugs, idarubicin has toxic side effects, so it isunlikely to ever be prescribed for patients fighting viralinfections. But, its identification demonstrates that the newstrategy works. "While idarubicin is not something you would give to a patient whohas the flu , we are continuing to screen more drugs," Patel says. "We'restarting to find compounds from different drug classes that are notso toxic and that have similar properties in enhancing interferonsignaling. We're still validating them, but we're very excitedabout what we're finding." Traditionally, techniques for drug discovery involve trying toenhance or inhibit a very specific interaction. To treat aparticular disease, scientists might try to disable a harmfulprotein, or replace a missing one, for example. But such approachesassume that altering a specific interaction of interest will resultin the desired effect. "I think our technique accepts the fact that we don't understandeverything that's going on in the cell," Patel says. "Instead oflooking at one particular interaction, we measure the downstreameffects." She compares it to driving a car and trying to make it go faster. "Traditionally, we would pick a specific part - a part of the carthat we think is responsible for speed - and then test compoundsthat alter the part in a way that we think will make the car gofaster," she says. "With our approach, we don't assume we know whatis responsible for speed. Instead, we take entire cars, treat themwith many different compounds, and just see which ones go faster." Patel says this screening technique is unusual because it canidentify drugs that enhance the body's own immune response to abroad range of viruses, unlike a vaccine, which only protectsagainst a specific virus. The method has also shed light on how some compounds with knownantiviral properties actually fight viruses. In addition to cancerdrugs, antidepressants and blood pressure medications, the initial64 drugs they identified with increased interferon activityincluded some known antiviral drugs. "We already knew some of these compounds had antiviral properties,we just didn't know why," Patel says. "Now we're starting to findout how they actually work." Additional References Citations. The e-commerce company in China offers quality products such as China Outdoor Led Flood Light Fixtures , China Flexible Led Ribbon Light, and more. For more , please visit Led Corn Light Bulb today!
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