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Editor, Senior Moderator
Sci Rep. 2018 Mar 15;8(1):4631. doi: 10.1038/s41598-018-22927-0.
[h=1]Stimulation of alpha2-adrenergic receptors impairs influenza virus infection.[/h] Matsui K[SUP]1,[/SUP][SUP]2[/SUP], Ozawa M[SUP]3[/SUP], Kiso M[SUP]4[/SUP], Yamashita M[SUP]4[/SUP], Maekawa T[SUP]1,[/SUP][SUP]2[/SUP], Kubota M[SUP]1,[/SUP][SUP]2[/SUP], Sugano S[SUP]1,[/SUP][SUP]5[/SUP], Kawaoka Y[SUP]6,[/SUP][SUP]7,[/SUP][SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A viruses cause seasonal epidemics and occasional pandemics. The emergence of viruses resistant to neuraminidase (NA) inhibitors and M2 ion channel inhibitors underlines the need for alternate anti-influenza drugs with novel mechanisms of action. Here, we report the discovery of a host factor as a potential target of anti-influenza drugs. By using cell-based virus replication screening of a chemical library and several additional assays, we identified clonidine as a new anti-influenza agent in vitro. We found that clonidine, which is an agonist of the alpha2-adrenergic receptor (α2-AR), has an inhibitory effect on the replication of various influenza virus strains. α2-AR is a Gi-type G protein-coupled receptor that reduces intracellular cyclic AMP (cAMP) levels. In-depth analysis showed that stimulation of α2-ARs leads to impairment of influenza virus replication and that α2-AR agonists inhibit the virus assembly step, likely via a cAMP-mediated pathway. Although clonidine administration did not reduce lung virus titers or prevent body weight loss, it did suppress lung edema and improve survival in a murine lethal infection model. Clonidine may thus protect against lung damage caused by influenza virus infection. Our results identify α2-AR-mediated signaling as a key pathway to exploit in the development of anti-influenza agents.
PMID: 29545586 DOI: 10.1038/s41598-018-22927-0
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[h=1]Stimulation of alpha2-adrenergic receptors impairs influenza virus infection.[/h] Matsui K[SUP]1,[/SUP][SUP]2[/SUP], Ozawa M[SUP]3[/SUP], Kiso M[SUP]4[/SUP], Yamashita M[SUP]4[/SUP], Maekawa T[SUP]1,[/SUP][SUP]2[/SUP], Kubota M[SUP]1,[/SUP][SUP]2[/SUP], Sugano S[SUP]1,[/SUP][SUP]5[/SUP], Kawaoka Y[SUP]6,[/SUP][SUP]7,[/SUP][SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A viruses cause seasonal epidemics and occasional pandemics. The emergence of viruses resistant to neuraminidase (NA) inhibitors and M2 ion channel inhibitors underlines the need for alternate anti-influenza drugs with novel mechanisms of action. Here, we report the discovery of a host factor as a potential target of anti-influenza drugs. By using cell-based virus replication screening of a chemical library and several additional assays, we identified clonidine as a new anti-influenza agent in vitro. We found that clonidine, which is an agonist of the alpha2-adrenergic receptor (α2-AR), has an inhibitory effect on the replication of various influenza virus strains. α2-AR is a Gi-type G protein-coupled receptor that reduces intracellular cyclic AMP (cAMP) levels. In-depth analysis showed that stimulation of α2-ARs leads to impairment of influenza virus replication and that α2-AR agonists inhibit the virus assembly step, likely via a cAMP-mediated pathway. Although clonidine administration did not reduce lung virus titers or prevent body weight loss, it did suppress lung edema and improve survival in a murine lethal infection model. Clonidine may thus protect against lung damage caused by influenza virus infection. Our results identify α2-AR-mediated signaling as a key pathway to exploit in the development of anti-influenza agents.
PMID: 29545586 DOI: 10.1038/s41598-018-22927-0
Free full text