Dengue cure lies in diabetes drugs

Scientists have identified enzymes and biochemical compounds called lipids that are targeted and modified by the dengue virus during infection. The findings suggest a potential new approach to control the aggressive mosquito-borne pathogen. The study indicates that medications used to treat high cholesterol and other lipid-related conditions might also inhibit dengue`s replication and could represent a potential new therapy. The researchers have identified how infected mosquito cells undergo changes to certain lipids in membranes and in biochemical sensors that alert cells of invading viruses. "The virus reorganizes the internal architecture of the cell to support its own needs," said Purdue University research scientist Rushika Perera. "Many details are unknown. This is our first attempt to understand how the virus alters lipids as part of the infection process. Part of what we looked at in this work was how the virus changes the cell, and the next step will be to figure out why," she explained. The researchers uncovered new details of how the virus alters lipids in membranes surrounding structures inside cells called organelles, including the mitochondria, which provide energy critical for a cell to function, and the endoplasmic reticulum, where proteins and lipids are synthesized. "Findings also show that important host enzymes are used by the virus and may be targets for future antiviral drugs," said Richard J. Kuhn, a professor and head of Purdue`s Department of Biological Sciences and director of the Bindley Bioscience Center. "It turns out, the pills you take to control your cholesterol might have some capability to control dengue," he added. The work was led by Perera in collaboration with researchers at Purdue`s Bindley Bioscience Center and the Pacific Northwest National Laboratory. The findings could apply to viruses similar to dengue, including the West Nile virus, yellow fever and hepatitis C. "Identifying pathways of infection will help us understand how these viruses work. Many viruses, including dengue, dramatically alter a host cell upon infection, and in this paper we begin to dissect the precise changes that occur. Ultimately, we are trying to understand how the virus subverts and exploits the host and uses it for its own purpose, which is to replicate," Kuhn said. The team learned specifically that an enzyme called fatty acid synthase, which cells use to synthesize lipids, is affected by the virus. Researchers showed that compounds inhibiting production of the enzyme also inhibit virus replication, suggesting drugs already on the market to treat diseases related to lipid synthesis and storage, including diabetes and cancer, also might be used to treat dengue, Kuhn said. The researchers had previously studied a compound that inhibits the production of fatty acid synthase in human cells. In the new findings, the researchers showed that the virus commandeers some of the same enzymes in both mosquito and human cells, meaning the same compound could work to attack the virus in mosquito cells. "This is important because it may be easier to control the virus in mosquitoes than in humans," Kuhn said. Findings of the study are detailed in the journal PLoS Pathogens.