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

• DOI: 10.1016/j.celrep.2016.12.068
• Publication Date: 2017-01-17T19:46:43Z
• Authors: Keiko Rausch; Brent A. Hackett; Nathan L. Weinbren; Sophia M. Reeder; Yoel Sadovsky; Christopher A. Hu...; David C. Schultz; Carolyn B. Coyne; Sara Cherry
• Keywords: Zika Virus; Flavivirus; Antibody-dependent enhancement

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 their ability to block infection in three distinct cell types with two different strains virus. Using microscopy-based assay, we validated 38 drugs that inhibited infection, including FDA-approved nucleoside analogs. Cells expressing high levels the attachment factor AXL can be protected from receptor tyrosine kinase inhibitors, while placental-derived cells lack expression insensitive this inhibition. Importantly, identified nanchangmycin as potent inhibitor entry across all tested, physiologically relevant primary cells. Nanchangmycin also was active against other medically viruses, West Nile, dengue, and chikungunya viruses use similar route entry. This study provides resource small molecules pathogenesis.