Identification of two HIV inhibitors that also inhibit human RNaseH2

A total of 140,000 compounds were screened in a targetfree cell-based high throughput assay against HIV-1 infection, and a subset of 81 promising compounds was identified. Secondary screening of these 81 compounds revealed two putative human RNaseH2 inhibitors, RHI001 and RHI002, with IC50 value of 6.8 mu M and 16 mu M, respectively. RHI002 showed selective activity against human RNaseH2 while RHI001 inhibited HIV-RNaseH, E. coli RNaseH, and human RNaseH1 with IC50 value of 28.5 mu M, 7.9 mu M, and 31.7 mu M, respectively. Kinetic analysis revealed that both inhibitors had non-competitive inhibitor-like properties. Because RNaseH2 is involved in the etiology of Aicardi-Goutier syndrome and has been suggested as an anticancer drug target, small molecule inhibitors modulating its activity would be useful for investigating the cellular function of this molecule.