High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1 PMID: 38844461

GLP-1 and Obesity Research

2026-08-18

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. [email protected].
9. Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, 730046, China. [email protected].
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. [email protected].
11. Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, 730046, China. [email protected].
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. [email protected].
13. Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, 730046, China. [email protected].

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.