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  • Poster presentation
  • Open Access

Impact of human immunodeficiency virus type 1 ribonuclease H inhibitors on the polymerase and RNase H function of foamy virus reverse transcriptase

  • 1,
  • 2,
  • 2,
  • 2,
  • 1 and
  • 2
Retrovirology201310 (Suppl 1) :P101

  • Published:


  • Efavirenz
  • Docking Experiment
  • Foamy Virus
  • Structural Overlay
  • Putative Binding Site


In foamy viruses (FVs) only the integrase domain is cleaved off from the Pol precursor protein, resulting in a multifunctional mature reverse transcriptase (RT) harbouring the protease (PR) domain at its N-terminus. In contrast to the heterodimeric RT of human immunodeficiency virus type 1 (HIV-1), which consists of a 66 kDa and a 51 kDa subunit, the PR-RT of FVs is a monomeric protein. Thus, we wanted to analyse the inhibitory effect of HIV-1 nonnucleoside and RNase H inhibitors on the enzyme functions of FV PR-RT.


We tested the effect of five HIV-1 RNase H inhibitors, known to interact with different HIV-1 RT pockets [1, 2], on the PR-RT of prototype FV (PFV). All compounds inhibited the PFV RNase H function at concentrations comparable to the ones reported for the HIV-1 RNase H, suggesting pocket similarity between the two proteins. In addition, four inhibitors also inhibited the PFV associated DNA polymerase activity. This can probably be attributed to differences in the protein’s structure and flexibility. The non-nucleoside RT inhibitor Efavirenz was inactive on PFV PR-RT, implying the absence of a binding pocket similar to the one in HIV-1 RT. NMR titration and in silico docking experiments with the free PFV RNase H domain and the diketo acid derivative RDS1463 identified a putative binding site reaching into the RNase H active site. Sequence alignments and structural overlays of HIV-1 and PFV RNase H were performed to identify the corresponding binding site in HIV-1 RNase H.


We showed that HIV-1 RNase H inhibitors are able to inhibit PFV PR-RT RNase H activity and in addition polymerase functions. NMR titration and docking experiments suggest a putative binding site for the RNase H inhibitor RDS 1643 close to the PFV RNase H active site.

Authors’ Affiliations

Department of Life and Environmental Sciences, University of Cagliari, Cittadella di Monserrato SS554, 09042 Monserrato, Cagliari, Italy
Lehrstuhl Biopolymere, Universität Bayreuth, Bayreuth, Germany


  1. Distinto S, Maccioni E, Meleddu R, Corona A, Alcaro S, Tramontano E: Molecular Aspects of the RT/drug Interactions. Perspective of Dual Inhibitors. Curr Pharrn Des. 2013, 19: 1850-1859. 10.2174/1381612811319100009.View ArticleGoogle Scholar
  2. Distinto S, Esposito F, Kirchmair J, Cardia MC, Gaspari M, Maccioni e, Alcaro S, Markt P, Wolber G, Zinzula L, Tramontano E: Identification of HIV-1 reverse transcriptase dual inhibitors by a combined shape-, 2D-fingerprint- and pharmacophore-based virtual screening approach. Eur J Med Chem. 2012, 50: 216-229.View ArticlePubMedGoogle Scholar


© Corona et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.