Open AccessTargeting the Respiratory Syncytial Virus N 0 -P Complex with Constrained α-Helical Peptides in Cells and Mice
Author(s) -
Marie Galloux,
Nadège Gsponer,
Vanessa Gaillard,
Brice Fenner,
Thibaut Larcher,
Marthe Vilotte,
Julie Rivière,
Charles-Adrien Richard,
Jean-François Éléouët,
Ronan Le Goffic,
Joëlle Mettier,
Origène Nyanguile
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00717-20
Subject(s) - mononegavirales , pneumovirinae , phosphoprotein , paramyxoviridae , virology , pneumovirus , virus , biology , viral replication , in vitro , in vivo , respiratory system , viral disease , gene , biochemistry , genetics , anatomy
Respiratory syncytial virus (RSV) is the main cause of severe respiratory infection in young children worldwide, and no therapies have been approved for the treatment of RSV infection. Data from recent clinical trials of fusion or L polymerase inhibitors for the treatment of RSV-infected patients revealed the emergence of escape mutants, highlighting the need for the discovery of inhibitors with novel mechanisms of action. Here we describe stapled peptides derived from the N terminus of the phosphoprotein (P) that act as replication inhibitors. We demonstrate that these peptides inhibit RSV replication in vitro and in vivo by preventing the formation of the N 0 -P complex. The present strategy provides a novel means of targeting RSV replication with constrained macrocyclic peptides or small molecules and is broadly applicable to other viruses of the Mononegavirales order.