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Updated: Jun 19, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
RNase H active site inhibitors of human immunodeficiency virus type 1 reverse transcriptase: design, biochemical
Thorsten A Kirschberg1, Mini Balakrishnan, Neil H Squires
1Department of Medicinal Chemistry, Gilead Sciences, Foster City, California 94404, USA. tkirschberg@gilead.com
Abstract:
Pyrimidinol carboxylic acids were designed as inhibitors of HIV-1 RNase H function. These molecules can coordinate to two divalent metal ions in the RNase H active site. Inhibition of enzymatic activity was measured in a biochemical assay, but no antiviral effect was observed. Binding was demonstrated via a solid state structure of the isolated p15-Ec domain of HIV-1 RT showing inhibitor and two Mn(II) ions bound to the RNase H active site.
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