title: Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin, Griffithsin.
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.
  
  
  RESULTS
  The new peptides derived from a trio of homologous β-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 EC(50) of 546.6±66.1 nM in p24gag 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 β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ewa D
authors.initials: ED
authors.lastname: Micewicz
authors.forename: Amy L
authors.initials: AL
authors.lastname: Cole
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Jung
authors.forename: Hai
authors.initials: H
authors.lastname: Luong
authors.forename: Martin L
authors.initials: ML
authors.lastname: Phillips
authors.forename: Pratikhya
authors.initials: P
authors.lastname: Pratikhya
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sharma
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Waring
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Cole
authors.forename: Piotr
authors.initials: P
authors.lastname: Ruchala
mesh_terms: D020418:Algal Proteins / Q000737:chemistry*; D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D015195:Drug Design; D016655:HIV Core Protein p24 / Q000737:chemistry; D023581:HIV Fusion Inhibitors / Q000494:pharmacology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010940:Plant Proteins; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D000461:Rhodophyta / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D020418:Algal Proteins; D004220:Disulfides; D016655:HIV Core Protein p24; D023581:HIV Fusion Inhibitors; D037102:Lectins; D010455:Peptides; D010940:Plant Proteins; C559061:grifonin-1 peptide, Griffithsia; C514799:p24 protein, Human Immunodeficiency Virus Type 1