Combinations of antiretroviral drugs are successfully used to treat HIV-infected
patients. However, drug resistance is a major problem that makes discovery of new antiretroviral
drugs an ongoing priority. The ribonuclease H (RNase H) activity of the HIV-1 reverse
transcriptase catalyzes the selective hydrolysis of the RNA strand of RNA:DNA heteroduplex
replication intermediates, and represents an attractive unexploited target for drug
development. This review reports on recent progress in the characterization of HIV-1
RNase H inhibitors from 2013 to 2016, describing their chemical structures, structureactivity
relationship and binding modes. Focus is given to emerging medicinal chemistry
principles and insights into the discovery and development of RNase H inhibitors.
Keywords: AIDS, HIV-1, RNase H inhibitors, dual inhibitors, drug design, SAR, antiviral, metalloenzyme.
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