Study uncovers secret behind HIV resistance to NNTRI antiretroviral drugs
Non-nucleoside reverse transcriptase inhibitor antiretroviral drugs slow the progression of the HIV infection, prolonging the life of the infected. For some, however, NNRTIs can cause the HIV virus to mutate, developing a resistance to the drugs.
The HIV virus grows in the body by manipulating an enzyme called reverse transcriptase, changing its genetic material into a single-stranded copy of its DNA, and then injecting that into an infected human cell. In time, the virus continues to spread until it overtakes the body as AIDS. NNTRIs, like efavirenz, inhibit this process by creating a salt bridge which prevents the reverse transcriptase from functioning.
"The reverse transcriptase can still bind the template, but it continually slides, preventing the enzyme from polymerizing nucleotides," Cell Biologist and Lead Author on the study Sanford Leuba said. "The virus cannot replicate."
The researchers for the first time discovered that the HIV virus can prevent the NNTRI from forming the salt bridge, thus allowing the reverse transcriptase to function normally without drug-binding affinity.
The research was presented at the 58th Annual Biophysical Society Meeting in San Francisco, California.
"We have ideas about how to begin designing a new generation of NNRTIs," Leuba said.