Unusual HIV Drug Resistance Revealed
(Ivanhoe Newswire) – New research from the University of Pittsburg School of Medicine shows how therapy with NNRTIs (non-nucleoside reverse transcriptase inhibitors) can lead to single (or “point”) mutations in the HIV genetic code, making the virus resistant to the drugs.
Researchers offer new insight into how NNRTIs function and how the mutations actually cause drug resistance. NNRTIs work by blocking action of an enzyme called reverse transcriptase. HIV uses this enzyme to convert its own genetic material into DNA, which can then be inserted into human cells they’ve infected. Once incorporated, this DNA tells the host to create new copies of the virus, which can lead to HIV/AIDS.
Using imaging techniques and computer modeling, researchers uncovered the binding of the NNRTI efavirenz formed a molecule-sized “salt bridge” during the DNA copying process. The researchers found point mutations that cause resistance to efavirenz prevent the salt bridge from forming. “This type of inhibition, which does not involve drug-binding affinity, has not been described previously,” cell biologist Sanford Leuba was quoted as saying.
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SOURCE: American Institute of Physics, February 2014
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