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Identification of two HIV inhibitors that also inhibit human RNaseH2 |
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| Authors: | Junghwan Kim Jaewan Yoon MoonKyeong Ju Yunmi Lee Tae-Hee Kim Junwon Kim Peter Sommer Zaesung No Jonathan Cechetto Sung-Jun Han |
| Affiliation: | 1. Drug Biology Group, Institut Pasteur Korea, Seongnam, 463-400, Korea 2. Screening Technology Platforms Group, Institut Pasteur Korea, Seongnam, 463-400, Korea 3. Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea 4. Medicinal Chemistry Group, Institute Pasteur Korea, Seongnam, 463-400, Korea 5. Cell Biology of Retroviruses Group, Institut Pasteur Korea, Seongnam, 463-400, Korea 6. Department of Biological Sciences, Konkuk University, Seoul, 143-701, Korea |
| Abstract: | 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 μM and 16 μM, 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 μM, 7.9 μM, and 31.7 μM, 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. |
| Keywords: | Aicardi-Goutier syndrome cell-based screening HIV inhibition human RNaseH2 |
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