Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus.

Autor:	Rausch K; Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA., Hackett BA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA., Weinbren NL; Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA., Reeder SM; Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA., Sadovsky Y; Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 19104, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 19104, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 19104, USA., Hunter CA; Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA., Schultz DC; High-Throughput Screening Core, University of Pennsylvania, Philadelphia, PA 19104, USA., Coyne CB; Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 19104, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 19104, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 19104, USA., Cherry S; Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: cherrys@mail.med.upenn.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2017 Jan 17; Vol. 18 (3), pp. 804-815.
DOI:	10.1016/j.celrep.2016.12.068
Abstrakt:	Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition. Importantly, we identified nanchangmycin as a potent inhibitor of Zika virus entry across all cell types tested, including physiologically relevant primary cells. Nanchangmycin also was active against other medically relevant viruses, including West Nile, dengue, and chikungunya viruses that use a similar route of entry. This study provides a resource of small molecules to study Zika virus pathogenesis. (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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