The antiviral activity of the antidepressant Prozac® elucidated

An antidepressant with antiviral properties

Back in 2013, in an initial collaboration with the Veterinary School of Utrecht University (Netherlands), researchers from the Emerging Viruses Unit and the Architecture and Function of Biological Macromolecules Laboratory had successfully demonstrated that fluoxetine had an antiviral effect in vitro on enteroviruses, a viral genus grouping together several human pathogens including the poliomyelitis, cold and hand-foot-and-mouth viruses.

In this new study, researchers have gone a step further in repositioning Prozac® to combat enterovirus infections. They sought to decipher how this drug, used as an antidepressant, could also prevent certain viruses from replicating. They first identified the viral protein targeted by fluoxetine, and then showed that the drug's antidepressant properties were not involved in its antiviral mode of action. This viral protein, known as 2C, is involved in the replication of the virus genome. By binding close to its active site, fluoxetine renders the protein inactive and viral replication is halted.

Strategy: repositioning existing drugs

This discovery shows that the strategy of repositioning drugs against viral pathologies for which there are no effective drugs can work. While the use of Prozac® to treat benign viral infections such as the common cold is out of the question, this work nevertheless opens up a number of avenues. Fluoxetine could be considered for the treatment of enterovirus infections with complications, particularly in immunocompromised individuals. Characterization of the mode of action at atomic level also opens the way to the development of new antiviral molecules specifically targeting the viral protein more effectively.