title: Identification of small molecules that interfere with H1N1 influenza A viral replication.
abstract: Successful replication of the influenza A virus requires both viral proteins and host cellular factors. In this study we used a cellular assay to screen for small molecules capable of interfering with any of such necessary viral or cellular components. We used an established reporter assay to assess influenza viral replication by monitoring the activity of co-expressed luciferase. We screened a diverse chemical compound library, resulting in the identification of compound 7, which inhibits a novel yet elusive target. Quantitative real-time PCR studies confirmed the dose-dependent inhibitory activity of compound 7 in a viral replication assay. Furthermore, we showed that compound 7 is effective in rescuing high-dose influenza infection in an in vivo mouse model. As oseltamivir-resistant influenza strains emerge, compound 7 could be further investigated as a new and potentially suitable scaffold for the development of anti-influenza agents that act on novel targets.
authors.affiliation: Infectious and Inflammatory Disease Center (IIDC) and Cancer Center (CC), Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Angel
authors.initials: A
authors.lastname: Bottini
authors.forename: Surya K
authors.initials: SK
authors.lastname: De
authors.forename: Bas J G
authors.initials: BJ
authors.lastname: Baaten
authors.forename: Bainan
authors.initials: B
authors.lastname: Wu
authors.forename: Elisa
authors.initials: E
authors.lastname: Barile
authors.forename: Stephen
authors.initials: S
authors.lastname: Soonthornvacharin
authors.forename: John L
authors.initials: JL
authors.lastname: Stebbins
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bradley
authors.forename: Sumit K
authors.initials: SK
authors.lastname: Chanda
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D054852:Small Molecule Libraries; D013777:Tetrazoles