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

Abstract

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.

• Authors: Keiko Rausch, Brent A Hackett, Nathan L Weinbren, Sophia M Reeder, Yoel Sadovsky, Christopher A Hunter, David C Schultz, Carolyn B Coyne, Sara Cherry
• Journal: Cell reports (Cell Rep) Vol. 18 Issue 3 Pg. 804-815 (01 17 2017) ISSN: 2211-1247 [Electronic] United States
• PMID: 28099856 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• Ethers
• Nucleosides
• Small Molecule Libraries
• Spiro Compounds
• nanchangmycin

Topics

• Antiviral Agents (chemistry, pharmacology)
• Cells, Cultured
• Chikungunya virus (drug effects)
• Dengue Virus (drug effects)
• Endothelial Cells (cytology, virology)
• Ethers (chemistry, pharmacology)
• Humans
• Nucleosides (chemistry, pharmacology)
• Small Molecule Libraries (chemistry, pharmacology)
• Spiro Compounds (chemistry, pharmacology)
• Trophoblasts (cytology, virology)
• Virus Internalization (drug effects)
• West Nile virus (drug effects)
• Zika Virus (drug effects, physiology)