Inhibition of Nipah Virus Infection In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry

• DOI: 10.1371/journal.ppat.1001168
• Publication Date: 2010-10-28T20:58:43Z
• Authors: Matteo Porotto; Barry Rockx; Christine C. Yoko...; Aparna Talekar; Ilaria DeVito; Laura M. Palermo; Jie Liu; Riccardo Cortese; Min Lu; Heinz Feldmann; Antonello Pessi; Anne Moscona
• Keywords: Heptad repeat; Lipopeptide; Viral membrane; Cell fusion

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions F have been shown inhibit by preventing formation of fusogenic six-helix bundle. We recently showed that addition a cholesterol group HRC peptides active against Nipah virus targets these where occurs, dramatically increasing their antiviral effect. this work, we report unlike untagged peptides, which bind postulated extended intermediate state bridging membranes, tagged HRC-derived interact with before peptide inserts into target membrane, thus capturing an earlier stage F-activation process. Furthermore, show tagging renders vivo: cholesterol-tagged cross blood brain barrier, effectively prevent treat established animal model what would otherwise be fatal encephalitis. The vivo efficacy particular ability penetrate CNS, suggests they are promising candidates for prevention or therapy infection other lethal paramyxoviruses.