HIV reverse transcriptase

Class

Non-nucleoside reverse transcriptase inhibitor (NNRTI)

HIV reverse transcriptase is a viral enzyme that copies the virus's single-stranded RNA genome into double-stranded DNA, a step required before the genetic material can integrate into a host cell's chromosome and establish infection. Because human cells have no equivalent enzyme, reverse transcriptase is an attractive and selective drug target. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a chemically diverse class of small molecules that bind a pocket on the enzyme distinct from the site where the natural building blocks of DNA are incorporated. This binding distorts the enzyme's shape and blocks its catalytic motion, halting DNA synthesis without needing to mimic a natural nucleotide. NNRTIs are used alongside nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), which block the same enzyme through a different, competitive mechanism, and often with a third class targeting a separate step of the viral life cycle. Combining agents that inhibit the same enzyme through different mechanisms, or that hit different life-cycle stages, raises the number of independent mutations the virus must accumulate to escape treatment, which is the biological rationale behind combination antiretroviral therapy. This mechanism is central to chronic suppression of HIV infection and to reducing transmission risk.