Compound is more potent than Tenofovir – one of the most used HIV drugs.
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 called EFdA 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 as similar existing drugs.”
EFdA is a nucleoside analog, similar to compounds that have functions ranging from flavor enhancers in soy sauce to drugs for the treatment of HIV and other viruses. EFdA was designed and synthesized by Hiroshi Ohrui (Chem Rec. 2006; 6 (3), 133-143; Org. Lett. 2011; 13, 5264) and shown by Hiroaki Mitsuya, Eiichi Kodama, and Yamasa to have potential usefulness against HIV and thus begun more than a decade of antiviral research on the compound.
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 Michael Parniak, professor of microbiology and molecular genetics at the University of Pittsburgh and Hiroaki Misuya, senior investigator at the HIV and AIDS Malignancy Branch at the 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.
“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.
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.”