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EDP-938，一种新型呼吸道合胞病毒核蛋白抑制剂，在体外和非人类灵长类动物模型中均显示出强大的抗病毒活性。

EDP-938, a novel nucleoprotein inhibitor of respiratory syncytial virus, demonstrates potent antiviral activities in vitro and in a non-human primate model.

机构信息

Enanta Pharmaceuticals Inc., Watertown, Massachusetts, United States of America.

Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.

出版信息

PLoS Pathog. 2021 Mar 15;17(3):e1009428. doi: 10.1371/journal.ppat.1009428. eCollection 2021 Mar.

DOI:10.1371/journal.ppat.1009428
PMID:33720995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7993833/
Abstract

EDP-938 is a novel non-fusion replication inhibitor of respiratory syncytial virus (RSV). It is highly active against all RSV-A and B laboratory strains and clinical isolates tested in vitro in various cell lines and assays, with half-maximal effective concentrations (EC50s) of 21, 23 and 64 nM against Long (A), M37 (A) and VR-955 (B) strains, respectively, in the primary human bronchial epithelial cells (HBECs). EDP-938 inhibits RSV at a post-entry replication step of the viral life cycle as confirmed by time-of-addition study, and the activity appears to be mediated by viral nucleoprotein (N). In vitro resistance studies suggest that EDP-938 presents a higher barrier to resistance compared to viral fusion or non-nucleoside L polymerase inhibitors with no cross-resistance observed. Combinations of EDP-938 with other classes of RSV inhibitors lead to synergistic antiviral activity in vitro. Finally, EDP-938 has also been shown to be efficacious in vivo in a non-human primate model of RSV infection.

摘要

EDP-938 是一种新型的非融合 RSV 复制抑制剂。它在体外的各种细胞系和检测中对所有 RSV-A 和 B 实验室株和临床分离株均具有高度活性，对 Long（A）、M37（A）和 VR-955（B）株的半数最大有效浓度（EC50）分别为 21、23 和 64 nM，在原代人支气管上皮细胞（HBECs）中。EDP-938 通过添加时间研究证实，在 RSV 生命周期的进入后复制步骤中抑制 RSV，并且该活性似乎由病毒核蛋白（N）介导。体外耐药性研究表明，与病毒融合或非核苷 L 聚合酶抑制剂相比，EDP-938 具有更高的耐药屏障，且未观察到交叉耐药性。EDP-938 与其他 RSV 抑制剂类别联合使用可在体外产生协同抗病毒活性。最后，EDP-938 还在 RSV 感染的非人类灵长类动物模型中显示出体内疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a20e/7993833/35b7af9316c5/ppat.1009428.g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a20e/7993833/31285c80b532/ppat.1009428.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a20e/7993833/1e159560bcbe/ppat.1009428.g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a20e/7993833/35b7af9316c5/ppat.1009428.g007.jpg

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