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

Cui Zhanding,Liu Jinlong,Xie Chong,Wang Tao,Sun Pu,Wang Jinlong,Li Jiaoyang,Li Guoxiu,Qiu Jicheng,Zhang Ying,Li Dengliang,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

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.