• 文献标题:   Discovery of direct-acting antiviral agents with a graphene-based fluorescent nanosensor
  • 文献类型:   Article
  • 作  者:   PARK SJ, KIM J, KANG S, CHA HJ, SHIN H, PARK J, JANG YS, WOO JS, WON C, MIN DH
  • 作者关键词:  
  • 出版物名称:   SCIENCE ADVANCES
  • ISSN:   2375-2548
  • 通讯作者地址:   Seoul Natl Univ
  • 被引频次:   0
  • DOI:   10.1126/sciadv.aaz8201
  • 出版年:   2020

▎ 摘  要

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.