title: C646, a Novel p300/CREB-Binding Protein-Specific Inhibitor of Histone Acetyltransferase, Attenuates Influenza A Virus Infection.
abstract: New strategies to develop novel broad-spectrum antiviral drugs against influenza virus infections are needed due to the emergence of antigenic variants and drug-resistant viruses. Here, we evaluated C646, a novel p300/CREB-binding protein-specific inhibitor of histone acetyltransferase (HAT), as an anti-influenza virus agent in vitro and in vivo and explored how C646 affects the viral life cycle and host response. Our studies highlight the value of targeting HAT activity for anti-influenza drug development.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuyama
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakai-Tagawa
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Takashita
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Shoemaker
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan kawaoka@ims.u-tokyo.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D004285:Dogs; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057809:HEK293 Cells; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009578:Nitrobenzenes; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D011720:Pyrazoles / Q000494:pharmacology*; D047069:Pyrazolones
chemical_list: C584509:4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid; D000998:Antiviral Agents; D001565:Benzoates; D009578:Nitrobenzenes; D011720:Pyrazoles; D047069:Pyrazolones; D050882:CREB-Binding Protein; D050881:E1A-Associated p300 Protein; D051548:Histone Acetyltransferases