Journal
NATURE BIOTECHNOLOGY
Volume 28, Issue 6, Pages 600-U88Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.1638
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Funding
- University of Hong Kong
- Research Fund for the Control of Infectious Diseases
- Area of Excellence Scheme of the University Grant Council [AoE/M-12/06]
- Hong Kong Sanatorium Hospital Doctors' Donation Fund
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Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains(1-5). Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly(6-9), creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC(50)) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies.
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