Cancer drug targets cell metabolism to fight flu

The influenza virus may be less likely to develop resistance to a drug that targets its effects on cell metabolism rather than a part of the virus itself. (CDC Influenza Laboratory)

While vaccines can ward off or dampen flu infection, the virus mutates so quickly that the shots need to be updated each year. Scientists at St. Jude Children’s Research Hospital have pinpointed a cancer drug that stops flu virus from replicating by targeting its effects on cell metabolism rather than the virus itself. It could provide an alternative treatment for flu infection.

The influenza virus co-opts cells lining the lungs, becoming “factories” that produce thousands of copies of the virus to spread infection. But “little was known about how flu infection changed the metabolism of lung epithelial cells,” said Paul Thomas, an associate member of the St. Jude Department of Immunology, in a statement.

Using PET scans, the team found a “dramatically increased” glucose metabolism in the lungs of 20 cancer patients with a weakened immune system who had the flu and other respiratory infections, compared to patients without infection. This metabolic change made the lung cells more dependent on glucose and glutamine, which are required for the virus to replicate.

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The researchers then looked at 80 drug candidates that attacked cell metabolism. They landed on several, including the investigational solid tumor drug BEZ235, which targets uncontrolled cell division by blocking a pair of metabolic pathways.

The drug reversed metabolic changes caused by infection, decreased the production of new virus, alleviated respiratory symptoms and improved survival in mice that were infected with a pandemic flu strain.

Currently, antiviral drugs may be used to lessen infection, but some strains have developed resistance to them. Researchers have previously tried to repurpose antivirals originally developed for other diseases. A team from Kansas State University, for example, found that Alferon N, which is used to treat genital warts, reduced the viral replication of Tamiflu-resistant H7N9 in a lab dish. But this approach still targets the virus, which can develop resistance.

“By focusing on changing how infected cells respond to the resulting metabolic stress rather than targeting a component of the virus itself, there is less risk that the virus will become resistant to the drugs,” Thomas said.

The St. Jude team plans to investigate cell metabolism in other respiratory viruses, including respiratory syncytial virus (RSV), which can cause serious infections in infants and the elderly.

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