美国哈佛医学院Jonathan Abraham等研究人员，合作揭示了尼帕病毒聚合酶复合物的结构与功能分析。相关论文于2025年1月20日在线发表在《细胞》杂志上。

研究人员通过冷冻电镜（cryo-EM）技术确定了尼帕病毒（NiV）聚合酶复合物的结构，该复合物由大蛋白（L）和磷蛋白（P）组成，并进行了NiV聚合酶的结构、生物物理学和深入功能分析。L蛋白与长的P四聚体卷曲螺旋结构组装，螺旋结构的末端由一束-螺旋结构所覆盖，研究人员表明这些结构在溶液中可能是动态的。

与已知L抑制剂的对接研究澄清了抗病毒药物抗药性机制。此外，研究人员还确定了L蛋白特征，这些特征对于转录和RNA复制都是必需的，并发现了对RNA复制影响大于转录的突变。这些研究结果有助于合理开发抗NiV感染的药物。

研究人员表示，NiV是一种由蝙蝠传播的、人畜共患的RNA病毒，对人类具有高度致病性。NiV聚合酶介导病毒基因组复制和mRNA转录，是一个有前景的药物靶点。

附：英文原文

Title: Structural and functional analysis of the Nipah virus polymerase complex

Author: Side Hu, Heesu Kim, Pan Yang, Zishuo Yu, Barbara Ludeke, Shawna Mobilia, Junhua Pan, Margaret Stratton, Yuemin Bian, Rachel Fearns, Jonathan Abraham

Issue&Volume: 2025-01-20

Abstract: Nipah virus (NiV) is a bat-borne, zoonotic RNA virus that is highly pathogenic in humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a promising drug target. We determined the cryoelectron microscopy (cryo-EM) structure of the NiV polymerase complex, comprising the large protein (L) and phosphoprotein (P), and performed structural, biophysical, and in-depth functional analyses of the NiV polymerase. The L protein assembles with a long P tetrameric coiled-coil that is capped by a bundle of -helices that we show are likely dynamic in solution. Docking studies with a known L inhibitor clarify mechanisms of antiviral drug resistance. In addition, we identified L protein features that are required for both transcription and RNA replication and mutations that have a greater impact on RNA replication than on transcription. Our findings have the potential to aid in the rational development of drugs to combat NiV infection.

DOI: 10.1016/j.cell.2024.12.021

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01434-X