Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin
Abbreviated Journal Title
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
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.
"Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin" (2010). Faculty Bibliography 2010s. 540.