한빛사논문
Se-Jin Park1, Jungho Kim1,2, Seounghun Kang1, Hyung Jin Cha1,3, Hojeong Shin1, Jisang Park4, Yong-Suk Jang4,5, Jae-Sung Woo3,6,*, Cheolhee Won2,* and Dal-Hee Min1,2,7,*
1Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.
2Institute of Biotherapeutics Convergence Technology, Lemonex Inc., Seoul 08826, Republic of Korea.
3Center for RNA Research, Institute for Basic Science (IBS), Seoul National University, Seoul 08826, Republic of Korea.
4Department of Bioactive Material Sciences and Institute of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Republic of Korea.
5Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Republic of Korea.
6Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
7Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
*Corresponding author.
Abstract
Direct-acting agents against viral components are considered as the most promising candidates for the successful antiviral therapeutics. To date, no direct-acting drugs exist for the treatment against dengue virus (DV) infection, which can develop into life-threatening diseases. RNA-dependent RNA polymerase (RdRp), an RNA virus–specific enzyme highly conserved among various viral families, has been known as the broad-range antiviral drug target. Here, we developed an RNA-based graphene biosensor system [RNA nano-graphene oxide system (RANGO)] to enable the fluorescence-based quantitative analysis of the RdRp enzyme activity. We used the RANGO system to a high-throughput chemical screening to identify novel direct-acting antiviral drug candidates targeting DV RdRp from the FDA-approved small-molecule library. RANGO accelerated the massive selection of drug candidates. We found that one of the selected hit compounds, montelukast, showed antiviral activity in vitro and in vivo by directly inhibiting replication of DV and thus relieved related symptoms.
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