期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 64, 期 10, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00717-20
关键词
N-0-P complex; RSV resistance mutants; antiviral agents; inhibitors; phosphoprotein; respiratory syncytial virus; stapled peptides
资金
- HES-SO University of Applied Sciences and Arts Western Switzerland RealTech Program [32324]
- Ark Foundation [314-10]
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.
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