Biological Evaluation of Molecules of the azaBINOL Class as Antiviral Agents: Specific Inhibition of HIV-1 RNase H Activity by 7-Isopropoxy-8-(naphth-1-yl)quinoline

Ross D. Overacker; Somdev Banerjee; George F. Neuhaus; Selena Milicevic Sephton; Alexander Herrmann; James A. Strother; Ruth Brack-Werner; Paul R. Blakemore; Sandra Loesgen

Promiscuous inhibitors in high-throughput screening endeavors often lead to unproductive 180 identification and development of compounds with non-specific activity. 36 For example, cell-181 based assays requiring a colorimetric out-read can be inhibited through non-specific mechanisms 182 giving false-positive results. 37 The cell-based HIVpp used in this study contains a luciferase 183 reporter out read, so we looked to test the capacity of B#24 to directly inhibit luciferase 184 luminescence in a recombinant luciferase enzyme test (SI Figure 6 ). 38 B#24 showed no inhibition 185 of luciferase activity nor quenching at any concentrations tested verifying that it was not acting 186 on luminescence. Additionally, based on the low solubility and largely hydrophobic surface area 187 of B#24, we sought to probe its ability to inhibit HIV-1 through unspecific aggregation effects. 188