28 July 2012

Antidepressants investigated for anti-viral, anti-fungal properties

by Will Parker

The antidepressant Zoloft has the potential to fight fungal meningitis, suggests a new study, while in separate research fluoxetine (commonly known as Prozac) has shown promise as an anti-viral agent for treating human enteroviruses.

The Zoloft (sertraline hydrocholoride) findings are the result of a two-year investigation by Texas A&M University's Xiaorong Lin. Lin examined Zoloft's effects on Cryptococcus neoformans, the major causative agent of fungal meningitis - specifically, cryptococcal meningitis, which claims more than half a million lives worldwide each year. The research appears in the journal Antimicrobial Agents and Chemotherapy.

Lin participated in a previous study to screen a collection of FDA-approved drugs to determine if any contained fungicidal agents. Although sertraline was shown to only moderately inhibit the effects of common fungal strains like Aspergillus nidulans, a genus of common mold often found on spoiled food, sertraline was found to be particularly effective against C. neoformans.

A follow-up investigation of sertraline in a mouse model of systemic cryptococcosis revealed that its efficacy is similar to fluconazole, an anti-fungal drug used commonly since the early 1990s. Moreover, a drug combination of sertraline and fluconazole was found to work more efficiently than either drug alone.

"The problem for many current anti-fungal drugs is that many cannot go to the brain, and it's very difficult for a lot of compounds to reach the brain in the first place," Lin explained. "So, you run into the problem of not killing all the fungus or having a very low level of fungus still exist. The fact is, this antidepressant can cross the blood-brain barrier and can get into the tissue at high concentrations."

It remains unclear exactly what dosage and concentration of sertraline is necessary to completely eliminate cryptococcosis, especially cryptococcal meningitis, but Lin's team hope those answers will come to light with further testing. "If this becomes useful, it could represent a truly significant increase in our ability to help people with brain cryptococcal infections," said co-researcher Matthew S. Sachs.

Meanwhile, researchers from UCLA say Prozac (fluoxetine) shows promise as an agent in treating human enteroviruses such as poliomyelitis and encephalitis. While immunization has all but eliminated the poliovirus, the archetype for the genus, no anti-viral drugs currently exist for the treatment of enterovirus infections, which are often severe and potentially fatal.

Interestingly, the researchers say that fluoxetine did not interfere with either viral entry or translation of the viral genome, but instead reduced the production of viral RNA and protein. The UCLA findings, as with the Texas A&M research, are detailed in the journal Antimicrobial Agents and Chemotherapy.

The UCLA team say the findings support the need for additional study into fluoxetine's potential as an anti-viral agent. "The discovery of unexpected anti-viral activity of fluoxetine is scientifically very significant," said UCLA's Robert Damoiseaux. "Part of our follow-up work will be the discovery of these unconventional targets for fluoxetine and other drugs of the same class and how these targets intersect with the known targets of this drug class."

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Source: University of California - Los Angeles, Texas A&M University