title: A novel small-molecule binds to the influenza A virus RNA promoter and inhibits viral replication.
abstract: Through screening by NMR spectroscopy, we discovered a novel scaffold (DPQ: 6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine) that binds specifically to the influenza A virus RNA promoter. The solution structure of the RNA-DPQ complex reported here demonstrates that the internal loop is the binding site of DPQ. The scaffold exhibits antiviral activity against influenza viruses.
authors.affiliation: Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195, USA. varani@chem.washington.edu.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Angel
authors.initials: A
authors.lastname: Bottini
authors.forename: Meehyein
authors.initials: M
authors.lastname: Kim
authors.forename: Michael F
authors.initials: MF
authors.lastname: Bardaro
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
authors.forename: Byong-Seok
authors.initials: BS
authors.lastname: Choi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Varani
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001665:Binding Sites; D004285:Dogs; D006860:Hydrogen Bonding; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D009690:Nucleic Acid Conformation; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C000590131:6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine; D000998:Antiviral Agents; D010879:Piperazines; D011799:Quinazolines; D012367:RNA, Viral