Anti-obesity drugs could halt viral infections

Viruses increase cellular metabolism to reproduce themselves, and some existing anti-obesity drugs can block these metabolic changes and nearly halt viral reproduction in infected cells, according to research recently published by scientists from Princetonnd the University of Rochester Medical Center.

“If you can prevent a virus from making copies, you have essentially stopped it,” said Bryson Bennett, a researcher from Princeton’s Lewis-Sigler Institute for Integrative Genomics. The use of the anti-obesity drugs led to a thousand-fold decrease in the ability of the virus to replicate, Bennett explained. “The real idea of the drug is to reduce the amount of the virus so that the immune system can take over.”

Bennett explained that normal cells have the machinery to break down blood sugars to produce lipids, particularly the fatty acids subgroup, which can be used in the creation of new cell membranes.

When viruses take control of a cell, however, they use the cell’s machinery for quick replication of viral cells. Certain viruses, such as human cytomegalovirus and Influenza-A, are lipid-coated viruses, which depend heavily on lipid production for replication. The lipid coatings of these viruses help them penetrate human cells.

The researchers investigated the way in which viral infection changes the rate of certain types of metabolism in the cell.

“Experiments were done that showed a quantitative increase in the production of fats in virus-infected cells,” said Anuraag Parikh ’08, who worked on the project under chemistry professor Joshua Rabinowitz.

The anti-obesity drugs are the key for blocking the metabolic changes that occur in viral cells. These drugs block the pathway in the cells that turns glucose into lipids, which are used for viral reproduction in infected cells. Though these drugs also stop the normal process of fatty acid biosynthesis, that process is not essential for adult humans.

Unlike many viral treatments that are specific to a single virus strand, this approach of targeting a particular pathway in the cell is applicable to many types of viruses. “It’s not normal for viruses that are so completely different to respond to the same type of treatment, and in that sense the findings are unusual,” Bennett said.

Important advancements in the areas of liquid chromatography and mass spectrometry enabled much of the research, Parikh said. “The kind of modeling we did was not really possible without the development of new scientific techniques ... which have allowed for more complex and informative data to be procured.”

Though the work in this study was primarily focused on viral infections, there may be important implications for other areas of medicine. “There is a certain class of diseases that are represented by large changes in the metabolism of cells,” Parikh said. “Cancer may be affected in the same way [as viruses], and it’s certainly useful to investigate this in the future.”

It will take years of additional research before new drugs based on this research can be offered on the market.

“Obviously our data on cell cultures suggest that there is potential for it to work, but lots of specific drugs with potential end up not working,” Bennett said. “The normal steps for any drug are to see if it works in animals, and if it does, then go on to see if it works in humans.”

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The experimental findings have been verified in rodents with promising results, but human trials have not yet begun.

Bennett and Parikh both noted the importance of inter-disciplinary research in this study. “This project was a collaboration between three groups: chemistry, metabolism and mass spectrometry, and virology,” Bennett said. “There is very much a trend in science with people in different fields of expertise working together to solve problems that they cannot solve on their own.”