Discovery of Novel Anti-prion Compounds Using In Silico and In Vitro Approaches

Jae Wook Hyeon, Jiwon Choi, Su Yeon Kim, Rajiv Gandhi Govindaraj, Kyu Jam Hwang, Yeong Seon Lee, Seong Soo A. An, Myung Koo Lee, Jong Young Joung, Kyoung Tai No, Jeongmin Lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Prion diseases are associated with the conformational conversion of the physiological form of cellular prion protein (PrPC) to the pathogenic form, PrPSc. Compounds that inhibit this process by blocking conversion to the PrPSc could provide useful anti-prion therapies. However, no suitable drugs have been identified to date. To identify novel anti-prion compounds, we developed a combined structure- and ligand-based virtual screening system in silico. Virtual screening of a 700,000-compound database, followed by cluster analysis, identified 37 compounds with strong interactions with essential hotspot PrP residues identified in a previous study of PrPC interaction with a known anti-prion compound (GN8). These compounds were tested in vitro using a multimer detection system, cell-based assays, and surface plasmon resonance. Some compounds effectively reduced PrPSc levels and one of these compounds also showed a high binding affinity for PrPC. These results provide a promising starting point for the development of anti-prion compounds.

Original languageEnglish
Article number14944
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Oct 9

All Science Journal Classification (ASJC) codes

  • General

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