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

Zhanding Cui, Jinlong Liu, Chong Xie, Tao Wang, Pu Sun, Jinlong Wang, Jiaoyang Li, Guoxiu Li, Jicheng Qiu, Ying Zhang, Dengliang Li, Ying Sun, Juanbin Yin, Kun Li, Zhixun Zhao, Hong Yuan, Xingwen Bai, Xueqing Ma, Pinghua Li, Yuanfang Fu, Huifang Bao, Dong Li, Qiang Zhang, Zaixin Liu, Yimei Cao (), Jing Zhang () and Zengjun Lu ()
Additional contact information
Zhanding Cui: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Jinlong Liu: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Chong Xie: University Medical Center Göttingen
Tao Wang: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Pu Sun: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Jinlong Wang: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Jiaoyang Li: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Guoxiu Li: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Jicheng Qiu: China Agricultural University
Ying Zhang: The Affiliated Animal Hospital of Jinzhou Medical University
Dengliang Li: Northwest Agriculture and Forestry University
Ying Sun: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Juanbin Yin: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Kun Li: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Zhixun Zhao: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Hong Yuan: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Xingwen Bai: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Xueqing Ma: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Pinghua Li: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Yuanfang Fu: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Huifang Bao: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Dong Li: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Qiang Zhang: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Zaixin Liu: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Yimei Cao: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Jing Zhang: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Zengjun Lu: Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48807-y

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