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HIV-1 RT-Associated RNase H Function Inhibitors: Recent Advances in Drug Development

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The HIV-1 genomic RNA reverse transcription is an essential step in the virus cycle carried out by the viral-coded reverse transcriptase (RT), which has two associated functions: the RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) function and the ribonuclease H (RNase H) function. The RNase H function catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate. The RT associated activities are both essential for HIV-1 replication and validated targets for drug development, but only the polymerase function has been widely investigated as drug target. In fact, either nucleoside or non-nucleoside RT inhibitors currently used in therapy act on the polymerase associated activity. In this review, we describe the compounds, reported up to today, which inhibit the HIV-1 RNase H function, their chemical structures, the structure-activity relationships and the mechanism of action.
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Keywords: HIV-1; RNase H; RNase H inhibitor; diketo acids; hydrazones; natural compounds; reverse transcriptase; ribonuclease H

Document Type: Research Article

Affiliations: Pasteur Institute - Fondazione Cenci Bolognetti, Dept. of Chemistry and Technology of Drug, “Sapienza” University of Rome, P.le Aldo Moro 5, I-00185 Rome, Italy.

Publication date: 2010-09-01

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