A compound found in soy sauce may be more potent than the current top antiviral therapy in fighting HIV, University of Missouri researchers have found. Seventy times stronger, in fact. 

The molecule was accidentally discovered by a Japanese soy sauce company in 2001 while trying to enhance the flavor of its product. The soy sauce molecule they isolated, EFdA, turns out to be part of the family of compounds called nucleoside analogues, which are 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.
Resistance to first-line drug therapy regimens is common in HIV patients being treated with anti-AIDS medications such as the anti-viral drug Tenofovir. Many are forced to adopt more potent medications.

“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,” he said.

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, according to MU scientists. 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 figure out how EFdA works on a molecular level. 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. “Not only does EFdA work on resistant HIV, it works better on HIV that has not become Tenofovir-resistant.”

The research was published the in the journals Retrovirology, Antimicrobial Agents and Chemotherapy and The International Journal of Pharmaceutics.

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