Discovery of direct-acting antiviral agents with a graphene-based fluorescent nanosensor

Se Jin Park, Jungho Kim, Jungho Kim, Seounghun Kang, Hyung Jin Cha, Hyung Jin Cha, Hojeong Shin, Jisang Park, Yong Suk Jang, Yong Suk Jang, Jae Sung Woo, Jae Sung Woo, Cheolhee Won, Dal Hee Min, Dal Hee Min, Dal Hee Min

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numberEAAZ8201
JournalScience Advances
Volume6
Issue number22
DOIs
Publication statusPublished - 2020 May

ASJC Scopus subject areas

  • General

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    Park, S. J., Kim, J., Kim, J., Kang, S., Cha, H. J., Cha, H. J., Shin, H., Park, J., Jang, Y. S., Jang, Y. S., Woo, J. S., Woo, J. S., Won, C., Min, D. H., Min, D. H., & Min, D. H. (2020). Discovery of direct-acting antiviral agents with a graphene-based fluorescent nanosensor. Science Advances, 6(22), [EAAZ8201]. https://doi.org/10.1126/sciadv.aaz8201