Abstract
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are chemically diverse compounds that allosterically inhibit HIV-1 reverse transcriptase (RT). NNRTIs are highly effective in the treatment of HIV-infected individuals when used in combination with other anti-HIV drugs. Recent studies have demonstrated that various NNRTIs can enhance, destabilize or have no effect on HIV-1 RT dimerization, suggesting that these drugs have different modes of binding to the HIV-1 RT. The strong enhancement of RT dimerization by many conventional NNRTIs such as efavirenz may contribute in part to the inhibitory activity of these drugs, while subunit destabilization by unconventional NNRTIs is thought to interfere with the RT heterodimerization-induced conformational changes that are essential for enzyme function. These studies suggest that modulation of subunit interaction by NNRTIs represents a previously unrecognized property of these RT inhibitors that could be exploited to produce more potent inhibitors of HIV-1 RT.