Inhibition of HIV‐1 by a Peptide Ligand of the Genomic RNA Packaging Signal Ψ

• DOI: 10.1002/cmdc.200700194
• Publication Date: 2008-01-18T15:23:40Z
• Authors: Julia Dietz; Joachim Koch; Ajit Kaur; Chinnappan Raja; Stefan Stein; Manuel Grez; Anette Pustowka; Sarah Mensch; Jan Ferner; Lars Möller; Norbert Bannert; Robert Tampé; Gilles Divita; Yves Mély; Harald Schwalbe; Ursula Dietrich
• Keywords: Group-specific antigen

The interaction of the nucleocapsid NCp7 human immunodeficiency virus type 1 (HIV-1) Gag polyprotein with RNA packaging signal Psi ensures specific encapsidation dimeric full length viral genome into nascent particles. Being an essential step in HIV-1 replication cycle, represents a promising target for therapeutic intervention. We previously selected peptides binding to Psi-RNA or stem loops (SL) thereof by phage display. Herein, we describe synthesis peptide variants consensus HWWPWW motif on membrane supports optimize binding. optimized peptide, psi-pepB, was characterized detail respect its conformation and properties SL3 NMR tryptophan fluorescence quenching. Functional analysis revealed that psi-pepB caused strong reduction release infected cells as monitored reduced transduction efficiencies, capsid p24 antigen levels, electron microscopy. Thus, this shows antiviral activity could serve lead compound develop new drugs targeting HIV-1.