Soy Sauce Molecule May Unlock Drug Therapy for HIV Patients, MU Researcher Finds
Compounds can be 70 times more potent than Tenofovir, a first-line HIV regimen
April 28, 2014 - COLUMBIA, Mo. - For HIV patients being treated with anti-AIDS medications, resistance to drug therapy
regimens is commonplace. Often, patients develop resistance to first-line drug therapies, such as Tenofovir, and are forced to adopt more
potent medications. Virologists at the University of Missouri now are testing the next generation of medications that stop HIV from
spreading, and are using a molecule related to flavor enhancers found in soy sauce, to develop compounds that are more potent than Tenofovir.
"Patients who are treated for HIV infections with Tenofovir, eventually develop resistance to the drugs that prevent an
effective or successful defense against the virus," said Stefan Sarafianos, associate professor of molecular microbiology and
immunology in the University of Missouri School of Medicine, and a virologist at the Bond Life Sciences Center
at MU. "EFdA, the molecule we are studying, is less likely to cause resistance in HIV patients because it is
more readily activated and is less quickly broken down by the body as similar existing drugs."
In 2001, a Japanese soy sauce company inadvertently discovered the EFdA molecule while trying to enhance the flavor of their
product. The flavor enhancer is part of the family of compounds called "nucleoside analogues" which is very similar to existing drugs
for the treatment of HIV and other viruses. EFdA samples were sent for further testing, which confirmed EFdA's potential usefulness
against HIV and started more than a decade of research.
EFdA, along with eight existing HIV drugs, is part of the class of compounds called nucleoside reverse transcriptase
inhibitors (NRTIs). NRTIs "hijack" the HIV replicating process by "tricking" building blocks inside the virus. Since EFdA appears
similar to those building blocks, the virus is misled into using the imposter, which prevents HIV replication and halts the
spread of the virus.
In their latest study, Sarafianos and his colleagues, including researchers from the University of Pittsburgh and the
National Institutes of Health, helped define how EFdA works on a molecular level. Using virology techniques and nuclear magnetic
resonance spectroscopy (NMR), they pieced together the exact structure and configuration of the molecule. Compounds developed
by Sarafianos and his team currently are being tested for usefulness as potential HIV-halting drugs with pharmaceutical company Merck.
"The structure of this compound is very important because it is a lock-and-key kind of mechanism that can be recognized by
the target," Sarafianos said. "EFdA works extremely well on HIV that is not resistant to anti-AIDS drugs, it also works even better on
HIV that's become resistant to Tenofovir."
Grants from the National Institutes of Health funded this research which was published the Journals Retrovirology,
Antimicrobial Agents and Chemotherapy and The International Journal of Pharmaceutics.
The rise of antibiotic-resistant superbugs, paired with a dwindling supply of effective antimicrobial drugs, has increased the threat
of infectious disease and created a healthcare crisis. If these findings are validated in humans, researchers may herald future medical
approaches to address the re-emerging crisis of infectious diseases.
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Editor's Note: For a longer version of this story, please visit "A drug that packs a punch: progress on new HIV compound proves usefulness against resistant virus."
Source: http://munews.missouri.edu/news-releases/2014/0428-soy-sauce-molecule-may-unlock-drug-therapy-for-hiv-patients-mu-researcher-finds/
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