Single-cycle Rift Valley fever virus particles from stable replicon cells enable discovery of antiviral CNX-1351 for multiple RNA viruses.

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica Pub Date : 2025-07-04 DOI:10.1016/j.virs.2025.06.009

Zhichao Gao, Hongyuan Guo, Ziqiao Wang, Pengcheng Wang, Xinran Sun, Shimei Zhang, Fei Feng, Chao Shan, Youhua Xie, Rong Zhang

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引用次数: 0

Abstract

Rift Valley fever virus (RVFV) is a high-containment pathogen that causes severe diseases in humans, with no approved therapeutics available. Its classification as a biosafety level 3 (BSL-3) agent has limited research and therapeutic development due to safety concerns. In this study, we developed a stable replicon cell line maintaining the replication of L and S genomic segments of RVFV. Single-cycle viral replicon particles (VRPs) could be efficiently packaged through trans-complementation of glycoproteins from different strains, recapitulating authentic viral entry and replication while minimizing biosafety risks. Using this system, we conducted high-throughput screening of a small-molecule compound library and identified CNX-1351 as an antiviral agent for multiple RNA viruses. Mechanistic studies revealed that CNX-1351 inhibits viral replication, potentially by targeting the PI3K-Akt signaling pathway. This single-cycle VRP system provides a valuable tool for studying RVFV biology, host interactions, antiviral and vaccine development under reduced biosafety constraints.

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来自稳定复制子细胞的单循环裂谷热病毒颗粒使多种RNA病毒的抗病毒药物CNX-1351得以发现。

裂谷热病毒（RVFV）是一种高度遏制的病原体，可在人类中引起严重疾病，目前尚无批准的治疗方法。由于安全方面的考虑，它被列为生物安全3级（BSL-3）药物，限制了研究和治疗开发。在这项研究中，我们开发了一种稳定的复制子细胞系，维持RVFV L和S基因组片段的复制。单循环病毒复制子颗粒（VRPs）可以通过不同菌株的糖蛋白的反式互补有效地包装，再现真实的病毒进入和复制，同时最大限度地降低生物安全风险。利用该系统，我们对一个小分子化合物文库进行了高通量筛选，并鉴定出CNX-1351作为多种RNA病毒的抗病毒药物。机制研究表明，CNX-1351可能通过靶向PI3K-Akt信号通路抑制病毒复制。这种单循环VRP系统为研究RVFV生物学、宿主相互作用、在生物安全限制降低的情况下开发抗病毒药物和疫苗提供了有价值的工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virologica Sinica Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

7.70

自引率

1.80%

发文量

3149

期刊介绍： Virologica Sinica is an international journal which aims at presenting the cutting-edge research on viruses all over the world. The journal publishes peer-reviewed original research articles, reviews, and letters to the editor, to encompass the latest developments in all branches of virology, including research on animal, plant and microbe viruses. The journal welcomes articles on virus discovery and characterization, viral epidemiology, viral pathogenesis, virus-host interaction, vaccine development, antiviral agents and therapies, and virus related bio-techniques. Virologica Sinica, the official journal of Chinese Society for Microbiology, will serve as a platform for the communication and exchange of academic information and ideas in an international context. Electronic ISSN: 1995-820X; Print ISSN: 1674-0769