非核苷类抑制剂ERDRP-0519抑制麻疹病毒聚合酶的结构基础

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-13 DOI:10.1038/s41467-025-64128-0

Dong Wang,Fan Bu,Ge Yang,Bin Liu

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引用次数: 0

摘要

ERDRP-0519是一种有效的抗麻疹病毒（MeV）和其他麻疹病毒的非核苷类抑制剂。在这里，我们报告了该化合物在2.73 Å和2.48 Å分辨率下与MeV聚合酶复合物结合的低温电镜结构，揭示了RdRp棕榈亚域中与催化GDN基元重叠的独特结合口袋。这些发现阐明了包括W671在内的耐药突变的基础，并为设计下一代副粘病毒抗病毒药物提供了基础。

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Structural basis of measles virus polymerase inhibition by nonnucleoside inhibitor ERDRP-0519.

ERDRP-0519 is a potent nonnucleoside inhibitor active against measles virus (MeV) and other Morbilliviruses. Here we report cryo-EM structures of the compound bound to MeV polymerase complexes at 2.73 Å and 2.48 Å resolution, revealing a unique binding pocket in the RdRp palm subdomain that overlaps the catalytic GDN motif. These findings clarify the basis of resistance mutations, including W671, and provide a foundation for designing next-generation Paramyxovirus antivirals.

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.