Open AccessStructural basis of antiviral activity of peptides from MPER of FIV gp36
Author(s) -
Manuela Grimaldi,
Ilaria Stillitano,
Giuseppina Amodio,
Angelo Santoro,
Michela Buonocore,
Ornella Moltedo,
Paolo Remondelli,
Anna Maria D’Ursi
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0204042
Subject(s) - feline immunodeficiency virus , peptide , lipid bilayer fusion , biology , lipid bilayer , cell membrane , lentivirus , biochemistry , chemistry , virology , microbiology and biotechnology , virus , membrane , viral disease
Feline immunodeficiency virus (FIV) is a naturally occurring Lentivirus causing acquired immunodeficiency syndrome in felines. It is considered a useful non-primate model to study HIV infection, and to test anti-HIV vaccine. Similarly to HIV, FIV enters cells via a mechanism involving a surface glycoprotein named gp36. C8 is a short synthetic peptide corresponding to the residues 770 WEDWVGWI 777 of gp36 membrane proximal external region (MPER). It elicits antiviral activity by inhibiting the fusion of the FIV and host cell membrane. C8 is endowed with evident membrane binding property, inducing alteration of the phospholipid bilayer and membrane fusion. The presence and the position of tryptophan residues in C8 are important for antiviral activity: the C8 derivative C6a, obtained by truncating the N-terminal 770 WE 771 residues, exhibits conserved antiviral activity, while the C8 derivative C6b, derived from the truncation of the C-terminal 776 WI 777 , is nearly inactive. To elucidate the structural factors that induce the different activity profiles of C6a and C6b, in spite of their similarity, we investigated the structural behaviour of the two peptides in membrane mimicking environments. Conformational data on the short peptides C6a and C6b, matched to those of their parent peptide C8, allow describing a pharmacophore model of antiviral fusion inhibitors. This includes the essential structural motifs to design new simplified molecules overcoming the pharmacokinetic and high cost limitations affecting the antiviral entry inhibitors that currently are in therapy.