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 N⁰-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.

中文翻译：

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用细胞和小鼠中的受限α-螺旋肽靶向呼吸道合胞病毒 N0-P 复合物。

呼吸道合胞病毒 (RSV) 是全球幼儿严重呼吸道感染的主要原因，目前尚未批准治疗 RSV 感染的疗法。最近用于治疗 RSV 感染患者的融合或 L 聚合酶抑制剂的临床试验数据揭示了逃逸突变体的出现，突出了发现具有新作用机制的抑制剂的必要性。在这里，我们描述了从磷蛋白 (P) 的 N 末端衍生的作为复制抑制剂的钉合肽。我们证明这些肽通过阻止 N ⁰的形成在体外和体内抑制 RSV 复制-P 复合物。本策略提供了一种用受限的大环肽或小分子靶向 RSV 复制的新方法，并且广泛适用于其他单倍体病毒目病毒。