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Research Article

Specific inhibition of the reverse transcriptase of human immunodeficiency virus type 1 and the chimeric enzymes of human immunodeficiency virus type 1 and type 2 by nonnucleoside inhibitors.

A Hizi, R Tal, M Shaharabany, M J Currens, M R Boyd, S H Hughes, J B McMahon
A Hizi
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
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R Tal
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
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M Shaharabany
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
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M J Currens
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
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M R Boyd
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
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S H Hughes
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
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J B McMahon
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
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DOI: 10.1128/AAC.37.5.1037
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ABSTRACT

We have studied the effects of four nonnucleoside inhibitors, including the novel natural product inhibitor calanolide A, on molecular chimeras containing complementary segments of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptases (RTs). All four compounds specifically inhibited the DNA polymerase activity of HIV-1 RT but had no apparent effect on the RNase H activity of this enzyme or on the DNA polymerase or RNase H activity of HIV-2 RT. Three of these compounds showed the generally expected patterns of resistance and susceptibility with the various chimeric RTs. However, the inhibition patterns of the chimeric RTs by calanolide A provided evidence that there is a segment between residues 94 and 157 in HIV-1 RT that is critical for inhibition. However, the data also suggest that there may be a second segment located between amino acids 225 and 427 in HIV-1 RT that is also important for specifying susceptibility to the drug.

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Specific inhibition of the reverse transcriptase of human immunodeficiency virus type 1 and the chimeric enzymes of human immunodeficiency virus type 1 and type 2 by nonnucleoside inhibitors.
A Hizi, R Tal, M Shaharabany, M J Currens, M R Boyd, S H Hughes, J B McMahon
Antimicrobial Agents and Chemotherapy May 1993, 37 (5) 1037-1042; DOI: 10.1128/AAC.37.5.1037

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Specific inhibition of the reverse transcriptase of human immunodeficiency virus type 1 and the chimeric enzymes of human immunodeficiency virus type 1 and type 2 by nonnucleoside inhibitors.
A Hizi, R Tal, M Shaharabany, M J Currens, M R Boyd, S H Hughes, J B McMahon
Antimicrobial Agents and Chemotherapy May 1993, 37 (5) 1037-1042; DOI: 10.1128/AAC.37.5.1037
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