title: 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: Institute of Molecular Virology (IMV), Centre of Molecular Virology (ZMBE), Westfälische Wilhelms-University, Münster, Germany.
authors: Rüdiger
authors: R
authors: Dierkes
authors: Institute of Molecular Virology (IMV), Centre of Molecular Virology (ZMBE), Westfälische Wilhelms-University, Münster, Germany.
authors: Kathrin
authors: K
authors: Warnking
authors: Institute of Molecular Virology (IMV), Centre of Molecular Virology (ZMBE), Westfälische Wilhelms-University, Münster, Germany.
authors: Swantje
authors: S
authors: Liedmann
authors: Institute of Molecular Virology (IMV), Centre of Molecular Virology (ZMBE), Westfälische Wilhelms-University, Münster, Germany.
authors: Roman
authors: R
authors: Seyer
authors: Institute of Molecular Virology (IMV), Centre of Molecular Virology (ZMBE), Westfälische Wilhelms-University, Münster, Germany.
authors: Stephan
authors: S
authors: Ludwig
authors: Institute of Molecular Virology (IMV), Centre of Molecular Virology (ZMBE), Westfälische Wilhelms-University, Münster, Germany.
authors: Christina
authors: C
authors: Ehrhardt
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry*; D017209:Apoptosis; D045744:Cell Line, Tumor; D004285:Dogs; D005260:Female; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000201:enzymology*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D011743:Pyrimidines / Q000737:chemistry*; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors*
chemical_list: D000634:Aminoquinolines; D000998:Antiviral Agents; C487513:NSC 23766; C061290:PA protein, influenza viruses; C502893:PB2 protein, influenza virus; D011743:Pyrimidines; C107953:RAC1 protein, human; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D012324:RNA-Dependent RNA Polymerase; D020830:rac1 GTP-Binding Protein