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Journal of Virology, February 2007, p. 2047-2055, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.01840-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Antiviral Peptides Targeting the West Nile Virus Envelope Protein{triangledown}

Fengwei Bai,1 Terrence Town,2 Deepti Pradhan,3 Jonathan Cox,1 Ashish,4 Michel Ledizet,5 John F. Anderson,6 Richard A. Flavell,2 Joanna K. Krueger,4 Raymond A. Koski,5 and Erol Fikrig1*

Section of Rheumatology, Department of Internal Medicine,1 Section of Immunobiology,2 Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520,3 Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28213,4 L2 Diagnostics, New Haven, Connecticut 06511,5 Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, Connecticut 065046

Received 23 August 2006/ Accepted 16 November 2006

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 µM 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 µM. 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.

* Corresponding author. Mailing address: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, The Anlyan Center for Medical Research and Education, Room S525A, 300 Cedar Street, P.O. Box 208031, New Haven, CT 06520-8031. Phone: (203) 785-2453. Fax: (203) 785-7053. E-mail: erol.fikrig{at}yale.edu.

{triangledown} Published ahead of print on 6 December 2006.

Journal of Virology, February 2007, p. 2047-2055, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.01840-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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