Abstract: The present invention discloses a nucleic acid cleavage assay for members of the transposase/integrase superfamily. A method of using the assay to screen for modulators of the nucleic acid cleavage activity is also disclosed. The present invention further provides a method for screening for modulators of binding of a transposase/integrase to its corresponding recognition sequence. In addition, the present invention provides a method of identifying a modulator for a particular transposase/integrase such as HIV integrase based on modulators of other members of the transposase/integrase superfamily. Also disclosed are Tn5 transposase inhibitors and HIV integration inhibitors.

Abstract: Cellular targets for anti-retroviral drug development are disclosed. The cellular targets comprise ATR kinase and its relevant substrates, based on the identification of the ATR kinase as required for the final step of retroviral DNA integration. Assays for identifying modulators of retroviral integration via the ATR kinase pathway are disclosed, as well as modulators identified by such assays. Pharmaceutical preparations and methods of their use in treating retroviral infection are also disclosed.