May 6, 2014
Treating HIV With Soy Sauce
I never cared much for Chinese food as a child, but all that changed around when I started going to college. From then on, I could not get enough of the stuff. Chinese food, Thai curry, sushi, I love it all. My gamer friends and I even have a weekly tradition that we simply call “Friday Thai-day,” as our Friday game night is hardly underway until we have stopped by a local carry-out Thai place to stuff ourselves on satay, curry, rice, and various other tasty goodies. For me, such a meal is always accompanied by a serving of plain, white rice that is season with a bit of soy sauce. While incredibly salty, I have always found its taste pleasing. Needless to say, it came as quite a surprise to discover that this tasty compliment was actually being used to develop the next generation of anti-AIDS medications.
Back in 2001, a Japanese soy sauce company called Yamasa discovered a molecule known as EFdA while they were trying to enhance the flavor of their sauce. This molecule was a part of a family of compounds called “nucleoside analogues” that are very similar to many existing drugs that are used in treating HIV, among other viruses. Yamasa sent EFdA samples off to be tested, which then prompted more than a decade of research. EFdA belongs to a class of compounds called nucleoside reverse transcriptase inhibitors, or “NRTIs” for short. NRTIs are already used for many HIV treatments. They work by disrupting the replication process of HIV by pretending to be the building blocks HIV uses to replicate itself. The virus thinks that the NRTI is what it needs to replicate and so it uses it, which then prevents its replication and halts its spread.
The current generation of anti-AIDS medications suffer from being too easy to resist. Patients will often develop resistance to first-line drug therapies to drugs such as Tenofovir, which force them to start taking more potent medications. Fortunately, EFdA molecules do not have this same problem. According to Stefan Sarafianos, as associate professor of molecular microbiology and immunology at the University of Missouri School of Medicine and virologist at the Bond Life Sciences Center at MU, “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. 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 their most recent study, Sarafianos and his colleagues sought to define how EFdA works. Using virology techniques and NMR (nuclear magnetic resonance spectroscopy), they were able to discern the exact structure and configuration of the molecule. “The structure of the compound is very important because it is the lock-and-key kind of mechanism that can be recognized by the target,” says Sarafianos. “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.” At present, compounds that were developed by Sarafianos and his team, which includes researchers from the University of Pittsburgh and the National Institutes of Health, are being tested for their usefulness as potential HIV-halting drugs with the help of the pharmaceutical company Merck.
Soy sauce. Who knew?
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