title: Antiviral peptides targeting the west nile virus envelope protein.
abstract: West Nile virus (WNV) can cause fatal murine and human encephalitis. The viral envelope protein interacts with host cells. A murine brain cDNA phage display library was therefore probed with WNV envelope protein, resulting in the identification of several adherent peptides. Of these, peptide 1 prevented WNV infection in vitro with a 50% inhibition concentration of 67 muM and also inhibited infection of a related flavivirus, dengue virus. Peptide 9, a derivative of peptide 1, was a particularly potent inhibitor of WNV in vitro, with a 50% inhibition concentration of 2.6 muM. Moreover, mice challenged with WNV that had been incubated with peptide 9 had reduced viremia and fatality compared with control animals. Peptide 9 penetrated the murine blood-brain barrier and was found in the brain parenchyma, implying that it may have antiviral activity in the central nervous system. These short peptides serve as the basis for developing new therapeutics for West Nile encephalitis and, potentially, other flaviviruses.
authors.affiliation: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Fengwei
authors.initials: F
authors.lastname: Bai
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
authors.forename: Deepti
authors.initials: D
authors.lastname: Pradhan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cox
authors.lastname: Ashish
authors.forename: Michel
authors.initials: M
authors.lastname: Ledizet
authors.forename: John F
authors.initials: JF
authors.lastname: Anderson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Krueger
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Koski
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002522:Chlorocebus aethiops; D003715:Dengue / Q000517:prevention & control; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D011485:Protein Binding; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors*; D014901:West Nile Fever / Q000517:prevention & control / Q000628:therapy; D014902:West Nile virus / Q000737:chemistry*
chemical_list: D019151:Peptide Library; D010455:Peptides; D014759:Viral Envelope Proteins