University of California, Los Angeles researchers have come across an unexpected potential use for
fluoxetine—commonly known as Prozac—which shows promise as an antiviral
agent. The discovery could provide another tool in treating human
enteroviruses that sicken and kill people in the U.S. and around the
world.
Human
enteroviruses are members of a genus containing more than 100 distinct
RNA viruses responsible for various life threatening infections, such as
poliomyelitis and encephalitis. While immunization has all but
eliminated the poliovirus, the archetype for the genus, no antiviral
drugs currently exist for the treatment of enterovirus infections, which
are often severe and potentially fatal. In view of its favorable
pharmacokinetics and safety profile of fluoxetine—which is in a class of
compounds typically used in the treatment of depression, anxiety
disorders and some personality disorders—the research team found that it
warrants additional study as a potential antiviral agent for
enterovirus infections.
Using
molecular screening, the UCLA research team from the Department of
Pediatrics, the California NanoSystems Institute and the Department of
Molecular and Medical Pharmacology found that fluoxetine was a potent
inhibitor of coxsackievirus replication. This is one of the viruses that
include polio and echovirus that is found in the gastrointestinal
tract. Exposure to the virus causes other opportunistic infections and
diseases.
“The
discovery of unexpected antiviral activity of fluoxetine is
scientifically very significant and draws our attention to previously
overlooked potential targets of fluoxetine and other psychogenic drugs,”
said Robert Damoiseaux, scientific director of the Molecular Screening
Shared Resource at the California NanoSystems Institute. “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.”
Paul
Krogstad, professor of pediatrics and molecular and medical
pharmacology, added that understanding the mechanisms of action of
fluoxetine and norfloxetine against coxsackieviruses “will add to our
understanding of enterovirus replication and lead to assessment of their
potential clinical utility for the future treatment of serious
enterovirus infections.”
The
research team found that fluoxetine did not interfere with either viral
entry or translation of the viral genome. Instead, fluoxetine and
norfluoxetine markedly reduced the production of viral RNA and protein.
The
study was published on July 2 in the journal of Antimicrobial Agents
and Chemotherapy. Study authors also include Jun Zuo, Kevin K. Quinn,
Steve Kye, and Paige Cooper from the Department of Pediatrics. The study
was supported by grants from the Today’s and Tomorrow’s Children’s Fund
and the UCLA Department of Pediatrics Nanopediatrics Program.
Source: University of California, Los Angeles
Filed Under: Drug Discovery
