Nipah virus (NiV) is a deadly zoonotic pathogen with high potential to cause another pandemic. Owing to biosafety concerns, studies on living NiV must be performed in biosafety level 4 (BSL-4) laboratories, which greatly hinders the development of anti-NiV drugs. To overcome this issue, minigenome systems have been developed to study viral replication and screen for antiviral drugs. This study aimed to develop two minigenome systems (transient and stable expression) based on a helper cell line expressing the NiV P, N and L proteins required to initiate NiV RNA replication. Stable minigenome cells were resistant to ribavirin, remdesivir and favipiravir but sensitive to interferons. Cells of the transient replication system were sensitive to ribavirin and favipiravir and suitable for drug screening. Our study demonstrates a feasible and effective platform for studying NiV replication and shows great potential for high-throughput drug screening in a BSL-2 laboratory environment.

中文翻译：

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建立新型小基因组系统用于鉴定针对尼帕病毒复制的药物

尼帕病毒 (NiV) 是一种致命的人畜共患病原体，极有可能引发另一场大流行。出于生物安全考虑，对活体NiV的研究必须在生物安全4级（BSL-4）实验室进行，这极大地阻碍了抗NiV药物的开发。为了克服这个问题，已经开发了小基因组系统来研究病毒复制和筛选抗病毒药物。本研究旨在开发两种基于辅助细胞系的微型基因组系统（瞬时表达和稳定表达），该辅助细胞系表达启动 NiV RNA 复制所需的 NiV P、N 和 L 蛋白。稳定的小基因组细胞对利巴韦林、瑞德西韦和法匹拉韦具有耐药性，但对干扰素敏感。瞬时复制系统的细胞对利巴韦林和法匹拉韦敏感，适合药物筛选。我们的研究展示了研究 NiV 复制的可行且有效的平台，并显示出在 BSL-2 实验室环境中进行高通量药物筛选的巨大潜力。