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

Authors: contact us about adding a copy of your work at [email protected]

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

Download

Share

COinS
 

Accessibility Statement

This item was created or digitized prior to April 24, 2027, or is a reproduction of legacy media created before that date. It is preserved in its original, unmodified state specifically for research, reference, or historical recordkeeping. In accordance with the ADA Title II Final Rule, the University Libraries provides accessible versions of archival materials upon request. To request an accommodation for this item, please submit an accessibility request form.