title: Inhibition of influenza virus replication by constrained peptides targeting nucleoprotein.
abstract: BACKGROUND
  Because of high mutation rates, new drug-resistant viruses are rapidly evolving, thus making the necessary control of influenza virus infection difficult.
  
  
  METHODS
  We screened a constrained cysteine-rich peptide library mimicking μ-conotoxins from Conus geographus and a proline-rich peptide library mimicking lebocin 1 and 2 from Bombyx mori by using influenza virus RNA polymerase (PB1, PB2 and PA) and nucleoprotein (NP) as baits.
  
  
  RESULTS
  Among the 22 peptides selected from the libraries, we found that the NP-binding proline-rich peptide, PPWCCCSPMKRASPPPAQSDLPATPKCPP, inhibited influenza replicon activity to mean±sd 40.7%±15.8% when expressed as a GFP fusion peptide in replicon cells. Moreover, when the GFP fusion peptide was transduced into cells by an HIV-TAT protein transduction domain sequence, the replication of influenza virus A/WSN/33 (WSN) at a multiplicity of infection of 0.01 was inhibited to 20% and 69% at 12 and 24 h post-infection, respectively. In addition, the TAT-GFP fusion peptide was able to slightly protect Balb/c mice from WSN infection when administrated prior to the infection.
  
  
  CONCLUSIONS
  These results suggest the potential of this peptide as the seed of an anti-influenza drug and reveal the usefulness of the constrained peptide strategy for generating inhibitors of influenza infection. The results also suggest that influenza NP, which is conserved among the influenza A viruses, is a good target for influenza inhibition, despite being the most abundant protein in infected cells.
authors.affiliation: Unit of Viral Genome Regulation, Institut Pasteur of Shanghai, Key Laboratory of Molecular Virology and Immunology, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Jiang
authors.forename: Yidong
authors.initials: Y
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Leiyun
authors.initials: L
authors.lastname: Weng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Shijian
authors.initials: S
authors.lastname: Zhang
authors.forename: Baosen
authors.initials: B
authors.lastname: Jia
authors.forename: Hongxing
authors.initials: H
authors.lastname: Hu
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacob
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Toyoda
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004285:Dogs; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007251:Influenza, Human / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014709:Vero Cells; D014758:Viral Core Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D019151:Peptide Library; D010455:Peptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins