HIV-1 reverse transcriptase inhibitors: beyond classic nucleosides and non-nucleosides. (May 2011)

• Record Type: Journal Article
• Authors: Scarth, Brian J; Ehteshami, Maryam; Beilhartz, Greg L; Göötte, Matthias
• Is Part Of: Future virology. Volume 6:Number 5(2011)
• Page Start: 581
• Page End: 598
• Publication Date: 2011-05
• Subjects: delayed chain terminator -- HIV -- NcRTI -- NNRTI -- NRTI -- reverse transcriptase -- RNase H inhibitors; Virology -- Periodicals; Virus diseases -- Treatment -- Periodicals; 616.9101
• DOI: 10.2217/fvl.11.35
• Languages: English
• ISSNs: 1746-0794

Abstract

Reverse transcriptase (RT) of HIV-1 remains an important target in current treatments of HIV-1 infection. Clinically available inhibitors of HIV-1 RT include nucleoside analog RT inhibitors and non-nucleoside RT inhibitors. Nucleoside analog RT inhibitors compete with the natural dNTP substrate and act as chain terminators, while non-nucleoside RT inhibitors bind to an allosteric pocket, inhibiting polymerization noncompetitively. In addition to these two classes of approved drugs, there are a number of RT inhibitors that target the enzyme in different ways. These include nonobligate chain terminators, nucleotide-competing RT inhibitors, pyrophosphate analogs and compounds that inhibit the RT-associated RNase H activity. Here, we review the mechanisms of action associated with these compounds and discuss opportunities and challenges in drug discovery and development efforts.