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

Nat Commun. 2024 Jun 6;15(1):4813. doi: 10.1038/s41467-024-48807-y.

Zhanding Cui ¹, Jinlong Liu ¹, Chong Xie ², Tao Wang ¹, Pu Sun ¹, Jinlong Wang ¹ ³, Jiaoyang Li ¹, Guoxiu Li ¹, Jicheng Qiu ⁴, Ying Zhang ⁵, Dengliang Li ⁶, Ying Sun ¹ ⁷, Juanbin Yin ¹, Kun Li ¹, Zhixun Zhao ¹, Hong Yuan ¹, Xingwen Bai ¹, Xueqing Ma ¹, Pinghua Li ¹, Yuanfang Fu ¹, Huifang Bao ¹, Dong Li ¹, Qiang Zhang ¹, Zaixin Liu ¹, Yimei Cao ⁸ ⁹, Jing Zhang ¹⁰ ¹¹, Zengjun Lu ¹² ¹³

Affiliations

1 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China.
2 Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.
3 Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
4 National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
5 The Affiliated Animal Hospital of Jinzhou Medical University, Jinzhou, China.
6 Veterinary Immunology Laboratory, College of Veterinary Medicine, Northwest Agriculture and Forestry University, Yangling, Shaanxi Province, 712100, China.
7 College of Veterinary Medicine, South China Agricultural University, No483 Wushan Road, TianheDistrict, Guangzhou, 510642, China.
8 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China. caoyimei@caas.cn.
9 Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, 730046, China. caoyimei@caas.cn.
10 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China. zhangjing@caas.cn.
11 Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, 730046, China. zhangjing@caas.cn.
12 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China. luzengjun@caas.cn.
13 Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, 730046, China. luzengjun@caas.cn.

PMID: 38844461 DOI: 10.1038/s41467-024-48807-y

Abstract

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-β 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.

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