A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus

Bersabeh Tigabu, Lynn Rasmussen, E. Lucile White, Nichole Tower, Mohammad Saeed, Alexander Bukreyev, Barry Rockx, James W. Leduc, James W. Noah

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalAssay and Drug Development Technologies
Volume12
Issue number3
DOIs
StatePublished - Apr 1 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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