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Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export

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  • Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export

    Cell Rep. 2019 May 7;27(6):1875-1885.e5. doi: 10.1016/j.celrep.2019.04.053.
    Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export.

    Zheng W1, Fan W1, Zhang S1, Jiao P2, Shang Y3, Cui L4, Mahesutihan M4, Li J1, Wang D5, Gao GF6, Sun L7, Liu W4.
    Author information

    Abstract

    Naproxen is a non-steroidal anti-inflammatory drug that has previously been shown to exert antiviral activity against influenza A virus by inhibiting nucleoprotein (NP) binding to RNA. Here, we show that naproxen is a potential broad, multi-mechanistic anti-influenza virus therapeutic, as it inhibits influenza B virus replication both in vivo and in vitro. The anti-influenza B virus activity of naproxen is more efficient than that of the commonly used neuraminidase inhibitor oseltamivir in mice. Furthermore, the NP of influenza B virus (BNP) has a higher binding affinity to naproxen than influenza A virus NP (ANP). Specifically, naproxen targets the NP at residues F209 (BNP) and Y148 (ANP). This interaction antagonizes the nuclear export of NP normally mediated by the host export protein CRM1. This study reveals a crucial mechanism of broad-spectrum anti-influenza virus activity of naproxen, suggesting that the existing drug naproxen may be used as an anti-influenza drug.
    Copyright ? 2019 The Authors. Published by Elsevier Inc. All rights reserved.


    KEYWORDS:

    CRM1; influenza virus; naproxen; nuclear export; nucleoprotein; vRNP

    PMID: 31067470 DOI: 10.1016/j.celrep.2019.04.053
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