Authors

E. D. Micewicz; A. L. Cole; C. L. Jung; H. Luong; M. L. Phillips; P. Pratikhya; S. Sharma; A. J. Waring; A. M. Cole;P. Ruchala

Comments

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Abbreviated Journal Title

PLoS One

Keywords

IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIVIRAL PROTEIN GRIFFITHSIN; INACTIVATING PROTEIN; SECONDARY STRUCTURE; CIRCULAR-DICHROISM; CARBOHYDRATE-BINDING; VIRAL PERSISTENCE; THETA-DEFENSIN; CYANOVIRIN-N; AMINO-ACIDS; Multidisciplinary Sciences

Abstract

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T-and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous beta-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8 +/- 11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6 +/- 66.1 nM in p24(gag) antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular beta-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1.

Journal Title

Plos One

Volume

5

Issue/Number

12

Publication Date

1-1-2010

Document Type

Article

Language

English

First Page

11

WOS Identifier

WOS:000285381200010

ISSN

1932-6203

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