High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1

文献类型： 外文期刊

第一作者： Cui, Zhanding

作者： Cui, Zhanding;Liu, Jinlong;Wang, Tao;Sun, Pu;Wang, Jinlong;Li, Jiaoyang;Li, Guoxiu;Sun, Ying;Yin, Juanbin;Li, Kun;Zhao, Zhixun;Yuan, Hong;Bai, Xingwen;Ma, Xueqing;Li, Pinghua;Fu, Yuanfang;Bao, Huifang;Li, Dong;Zhang, Qiang;Liu, Zaixin;Cao, Yimei;Zhang, Jing;Lu, Zengjun;Xie, Chong;Wang, Jinlong;Qiu, Jicheng;Zhang, Ying;Li, Dengliang;Sun, Ying;Cao, Yimei;Zhang, Jing;Lu, Zengjun

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期刊名称：NATURE COMMUNICATIONS （ 影响因子：14.7； 五年影响因子：16.1 ）

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年卷期： 2024 年 15 卷 1 期

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收录情况： SCI

摘要： Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ's role in augmenting the sensitivity of the IFN-beta pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ's effectiveness. There are limited prevention or treatment options for PRRSV. Here, the authors identified nitazoxanide as a promising inhibitor of PRRSV and demonstrate its antiviral efficacy in reducing PRRSV replication and transmission in vivo.

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