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Abstract
<p class="first" id="d16305777e193">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.
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