Considerations for structure-based drug design targeting hiv-1 reverse transcriptase

Eddy Arnold, Sergio E. Martinez, Joseph D. Bauman, Kalyan Das

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations


HIV-1 reverse transcriptase (RT) copies the viral single-stranded RNA genome into a double-stranded DNA version, and is a central target for anti-AIDS therapeutics. Eight nucleoside/nucleotide analogs (NRTIs) and five non-nucleoside inhibitors (NNRTIs) are approved HIV-1 drugs. Structures of RT have been determined in complexes with substrates and/or inhibitors, and the structures have revealed different conformational and functional states of the enzyme. Rilpivirine and etravirine, two NNRTI drugs with high potency against common resistant variants, were discovered and developed through a multidisciplinary structure-based drug design effort. The resilience of rilpivirine and etravirine to resistance mutations results from the structural flexibility and compactness of these drugs. Recent insights into mechanisms of inhibition by the allosteric NNRTIs include (i) dynamic sliding of RT/NNRTI complexes along template-primers and (ii) displacement of the RT primer grip that repositions the 30-primer terminus away from the polymerase active site.

Original languageAmerican English
Title of host publicationMultifaceted Roles of Crystallography in Modern Drug Discovery
PublisherSpringer Netherlands
Number of pages13
ISBN (Electronic)9789401797191
ISBN (Print)9789401797184
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)


Dive into the research topics of 'Considerations for structure-based drug design targeting hiv-1 reverse transcriptase'. Together they form a unique fingerprint.

Cite this