Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that continues to cause outbreaks in humans characterized by high mortality and significant clinical sequelae in survivors. Currently, no therapeutics are approved for use in humans against NiV infection. Here, we report that 4'-chloromethyl-2'-deoxy-2'-fluorocytidine (ALS-8112) inhibits NiV. ALS-8112 is the parent nucleoside of lumicitabine, which has been evaluated in phase I and II clinical trials to treat pediatric and adult respiratory syncytial virus infection. In this study, we tested ALS-8112 against NiV and other major human respiratory pneumo- and paramyxoviruses in 2 human lung epithelial cell lines, and demonstrated the ability of ALS-8112 to reduce infectious wild-type NiV yield by over 6 orders of magnitude with no apparent cytotoxicity. However, further cytotoxicity testing in primary cells and bone marrow progenitor cells indicated cytotoxicity at higher concentrations of ALS-8112. Our results warrant the evaluation of lumicitabine against NiV infection in relevant animal models.

中文翻译：

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β-D-4'-氯甲基-2'-脱氧-2'-氟胞苷对尼帕病毒具有有效的体外活性。

尼帕病毒（NiV）是一种高致病性人畜共患副粘病毒，持续在人类中引起疫情暴发，其特点是死亡率高，幸存者会出现严重的临床后遗症。目前，还没有批准用于人类对抗 NiV 感染的疗法。在此，我们报告 4'-氯甲基-2'-脱氧-2'-氟胞苷 (ALS-8112) 可以抑制 NiV。ALS-8112 是 lumicitabine 的母体核苷，已在治疗儿童和成人呼吸道合胞病毒感染的 I 期和 II 期临床试验中进行了评估。在这项研究中，我们在 2 种人肺上皮细胞系中测试了 ALS-8112 对抗 NiV 和其他主要人类呼吸道肺炎病毒和副粘病毒的能力，并证明 ALS-8112 能够将传染性野生型 NiV 产量降低 6 个数量级以上无明显细胞毒性。然而，对原代细胞和骨髓祖细胞的进一步细胞毒性测试表明，较高浓度的 ALS-8112 具有细胞毒性。我们的结果支持在相关动物模型中评估鲁米他滨对抗 NiV 感染的作用。