The Rac1 inhibitor NSC23766 exerts anti-influenza virus properties by affecting the viral polymerase complex activity.

Abstract	The frequent emergence of new influenza viruses in the human population underlines the urgent need for antiviral therapeutics in addition to the preventative vaccination against the seasonal flu. To circumvent the development of resistance, recent antiviral approaches target cellular proteins needed by the virus for efficient replication. We investigated the contribution of the small GTPase Rac1 to the replication of influenza viruses. Inhibition of Rac1 by NSC23766 resulted in impaired replication of a wide variety of influenza viruses, including a human virus strain of the pandemic from 2009 as well as highly pathogenic avian virus strains. Furthermore, we identified a crucial role of Rac1 for the activity of the viral polymerase complex. The antiviral potential of NSC23766 was confirmed in mouse experiments, identifying Rac1 as a new cellular target for therapeutic treatment of influenza virus infections.
Authors	Rüdiger Dierkes, Kathrin Warnking, Swantje Liedmann, Roman Seyer, Stephan Ludwig, Christina Ehrhardt
Journal	PloS one (PLoS One) Vol. 9 Issue 2 Pg. e88520 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID	24523909 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Aminoquinolines Antiviral Agents NSC 23766 PA protein, influenza viruses PB2 protein, influenza virus Pyrimidines RAC1 protein, human Viral Proteins influenza virus polymerase basic protein 1 RNA-Dependent RNA Polymerase rac1 GTP-Binding Protein
Topics	Aminoquinolines (chemistry) Animals Antiviral Agents (chemistry) Apoptosis Cell Line, Tumor Dogs Female Humans Madin Darby Canine Kidney Cells Male Mice Mice, Inbred BALB C Orthomyxoviridae (enzymology) Orthomyxoviridae Infections (drug therapy) Pyrimidines (chemistry) RNA-Dependent RNA Polymerase (metabolism) Signal Transduction Viral Proteins (metabolism) rac1 GTP-Binding Protein (antagonists & inhibitors)

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