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Mol. Cells 2013; 36(3): 212-218

Published online September 30, 2013

https://doi.org/10.1007/s10059-013-2348-z

© The Korean Society for Molecular and Cellular Biology

Identification of Two HIV Inhibitors that also Inhibit Human RNaseH2

Junghwan Kim, Jaewan Yoon, MoonKyeong Ju, Yunmi Lee, Tae-Hee Kim, Junwon Kim, Peter Sommer, Zaesung No, Jonathan Cechetto, and Sung-Jun Han

1Drug Biology Group, 2Screening Technology Platforms Group, Institut Pasteur Korea, Seongnam 463-400, Korea, 3Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea, 4Medicinal Chemistry Group, Institute Pasteur Korea, Seongnam 463-400, Korea, 5Cell Biology of Retroviruses Group, Institut Pasteur Korea, Seongnam 463-400, Korea, 6Department of Biological Sciences, Konkuk University, Seoul 143-701, Korea

Received: December 28, 2013; Revised: July 1, 2013; Accepted: July 3, 2013

Abstract

A total of 140,000 compounds were screened in a target-free 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 ?M and 16 ?M, respec-tively. RHI002 showed selective activity against human RNaseH2 while RHI001 inhibited HIV-RNaseH, E. coli RNaseH, and human RNaseH1 with IC50 value of 28.5 ?M, 7.9 ?M, and 31.7 ?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.

Keywords Aicardi-Goutier syndrome, cell-based screening, HIV inhibition, human RNaseH2

Article

Research Article

Mol. Cells 2013; 36(3): 212-218

Published online September 30, 2013 https://doi.org/10.1007/s10059-013-2348-z

Copyright © The Korean Society for Molecular and Cellular Biology.

Identification of Two HIV Inhibitors that also Inhibit Human RNaseH2

Junghwan Kim, Jaewan Yoon, MoonKyeong Ju, Yunmi Lee, Tae-Hee Kim, Junwon Kim, Peter Sommer, Zaesung No, Jonathan Cechetto, and Sung-Jun Han

1Drug Biology Group, 2Screening Technology Platforms Group, Institut Pasteur Korea, Seongnam 463-400, Korea, 3Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea, 4Medicinal Chemistry Group, Institute Pasteur Korea, Seongnam 463-400, Korea, 5Cell Biology of Retroviruses Group, Institut Pasteur Korea, Seongnam 463-400, Korea, 6Department of Biological Sciences, Konkuk University, Seoul 143-701, Korea

Received: December 28, 2013; Revised: July 1, 2013; Accepted: July 3, 2013

Abstract

A total of 140,000 compounds were screened in a target-free 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 ?M and 16 ?M, respec-tively. RHI002 showed selective activity against human RNaseH2 while RHI001 inhibited HIV-RNaseH, E. coli RNaseH, and human RNaseH1 with IC50 value of 28.5 ?M, 7.9 ?M, and 31.7 ?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.

Keywords: Aicardi-Goutier syndrome, cell-based screening, HIV inhibition, human RNaseH2

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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