The mammarenavirus Lassa (LASV) is highly prevalent in West Africa where it infects several hundred thousand individuals annually resulting in a high number of Lassa fever (LF) cases, a febrile disease associated with high morbidity and significant mortality. Mounting evidence indicates that the worldwide-distributed prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. There are not Food and Drug Administration (FDA) licensed vaccines and current anti-mammarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective and can cause significant side effects. Therefore, there is an unmet need for novel antiviral drugs to combat LASV. This task would be facilitated by the implementation of high throughput screens (HTS) to identify inhibitors of the activity of the virus ribonucleoprotein (vRNP) responsible for directing virus RNA genome replication and gene transcription. The use of live LASV for this purpose is jeopardized by the requirement of biosafety level 4 (BSL4) containment. We have developed a virus-free cell platform, where expression levels of reporter genes serve as accurate surrogates of vRNP activity, to develop cell-based assays compatible with HTS to identify inhibitors of LASV and LCMV mammarenavirus vRNP activities.

中文翻译：

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一种基于细胞、无传染性的平台，用于识别拉沙病毒核糖核蛋白 (vRNP) 活性的抑制剂。


乳腺病毒拉沙病毒 (LASV) 在西非非常流行，每年感染数十万人，导致大量拉沙热 (LF) 病例，这是一种发病率高、死亡率高的发热性疾病。越来越多的证据表明，世界范围内分布的原型乳房病毒淋巴细胞性脉络膜脑膜炎病毒（LCMV）是一种被忽视的具有临床意义的人类病原体。目前尚无美国食品和药物管理局 (FDA) 许可的疫苗，并且目前的抗乳房病毒疗法仅限于超说明书使用利巴韦林，这种疗法仅部分有效，并可能导致严重的副作用。因此，对抗 LASV 的新型抗病毒药物的需求尚未得到满足。通过实施高通量筛选 (HTS) 来识别负责指导病毒 RNA 基因组复制和基因转录的病毒核糖核蛋白 (vRNP) 活性的抑制剂，将有助于这项任务。为此目的使用活 LASV 会受到生物安全 4 级 (BSL4) 遏制要求的影响。我们开发了一个无病毒细胞平台，其中报告基因的表达水平可作为 vRNP 活性的准确替代物，以开发与 HTS 兼容的基于细胞的测定法，以识别 LASV 和 LCMV 哺乳动物病毒 vRNP 活性的抑制剂。