A high throughput screen identifies benzoquinoline compounds as inhibitors of Ebola virus replication

Priya Luthra, Jue Liang, Colette A. Pietzsch, Sudip Khadka, Megan R. Edwards, Shuguang Wei, Sampriti De, Bruce Posner, Alexander Bukreyev, Joseph M. Ready, Christopher F. Basler

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Ebola virus (EBOV) is an enveloped negative-sense, single-stranded RNA virus of the filovirus family that causes severe disease in humans. Approved therapies for EBOV disease are lacking. EBOV RNA synthesis is carried out by a virus-encoded complex with RNA-dependent RNA polymerase activity that is required for viral propagation. This complex and its activities are therefore potential antiviral targets. To identify potential lead inhibitors of EBOV RNA synthesis, a library of small molecule compounds was screened against a previously established assay of EBOV RNA synthesis, the EBOV minigenome assay (MGA), in 384 well microplate format. The screen identified 56 hits that inhibited EBOV MGA activity by more than 70% while exhibiting less than 20% cell cytotoxicity. Inhibitory chemical scaffolds included angelicin derivatives, derivatives of the antiviral compound GSK983 and benzoquinolines. Structure-activity relationship (SAR) studies of the benzoquinoline scaffold produced ∼50 analogs and led to identification of an optimized compound, SW456, with a submicromolar IC50 in the EBOV MGA and antiviral activity against infectious EBOV in cell culture. The compound was also active against a MGA for another deadly filovirus, Marburg virus. It also exhibited antiviral activity towards a negative-sense RNA virus from the rhabdovirus family, vesicular stomatitis virus, and a positive-sense RNA virus, Zika virus. Overall, these data demonstrate the potential of the EBOV MGA to identify anti-EBOV compounds and identifies the benzoquinoline series as a broad-spectrum antiviral lead.

Original languageEnglish (US)
Pages (from-to)193-201
Number of pages9
JournalAntiviral research
StatePublished - Feb 2018


  • Antiviral
  • Ebola virus
  • Filovirus
  • Marburg virus
  • Vesicular stomatitis virus
  • Zika virus

ASJC Scopus subject areas

  • Pharmacology
  • Virology


Dive into the research topics of 'A high throughput screen identifies benzoquinoline compounds as inhibitors of Ebola virus replication'. Together they form a unique fingerprint.

Cite this