Deutsch
 
Benutzerhandbuch Datenschutzhinweis Impressum Kontakt
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection

MPG-Autoren
/persons/resource/persons78058

Habjan,  Matthias
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

Externe Ressourcen
Es sind keine Externen Ressourcen verfügbar
Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Islam, M. K., Baudin, M., Eriksson, J., Öberg, C., Habjan, M., Weber, F., et al. (2016). High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection. JOURNAL OF BIOMOLECULAR SCREENING, 21(4), 354-362. doi:10.1177/1087057115625184.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002A-6BE0-7
Zusammenfassung
Rift Valley fever virus (RVFV) is an emerging virus that causes serious illness in humans and livestock. There are no approved vaccines or treatments for humans. The purpose of the study was to identify inhibitory compounds of RVFV infection without any preconceived idea of the mechanism of action. A whole-cell-based high-throughput drug screening assay was developed to screen 28,437 small chemical compounds targeting RVFV infection. To accomplish both speed and robustness, a replication-competent NSs-deleted RVFV expressing a fluorescent reporter gene was developed. Inhibition of fluorescence intensity was quantified by spectrophotometry and related to virus infection in human lung epithelial cells (A549). Cell toxicity was assessed by the Resazurin cell viability assay. After primary screening, 641 compounds were identified that inhibited RVFV infection by 80%, with 50% cell viability at 50 mu M concentration. These compounds were subjected to a second screening regarding dose-response profiles, and 63 compounds with 60% inhibition of RVFV infection at 3.12 mu M compound concentration and 50% cell viability at 25 mu M were considered hits. Of these, six compounds with high inhibitory activity were identified. In conclusion, the high-throughput assay could efficiently and safely identify several promising compounds that inhibited RVFV infection.