猪繁殖与呼吸综合征（Porcine Reproductive and Respiratory Syndrome, PRRS）对全球养猪业构成重大威胁。PRRS由猪繁殖与呼吸综合征病毒（PRRSV）引起，主要影响母猪的生殖系统和仔猪的呼吸系统，导致高死亡率和重大经济损失。PRRSV的高度变异性使其难以控制，现有疫苗策略存在局限性，无法提供足够的保护，且弱毒疫苗存在安全隐患。因此，迫切需要开发新的预防和治疗措施来应对这一挑战。

中国农业科学院兰州兽医研究所卢曾军/曹轶梅团队在国际期刊Nature Communications发表了题为“High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1”的研究论文。

本研究通过高通量筛选技术从FDA批准的药物库中鉴定出16种潜在的抗PRRSV化合物。其中Nitazoxanide (NTZ)是一种有效的猪繁殖和呼吸综合征病毒(PRRSV)抑制剂，NTZ在体外和体内模型中都显示出减少PRRSV增殖和传播的强大效果，能够缓解病毒血症和肺部损伤。

图1: NTZ能够显著减少PRRSV的增殖和传播，缓解病毒血症和肺部损伤，降低临床症状和死亡率。

NTZ的主要代谢产物Tizoxanide是NMRAL1二聚体形成的促进剂，这可能揭示了TIZ增强干扰素-β (IFN-β)途径敏感性，从而提高宿主对PRRSV的抗病毒反应； NTZ在猪体内显示出良好的药代动力学特性和组织分布，且在高剂量下未观察到明显不良反应，表明其具有较高的安全性； 分子对接和动力学模拟， 确认了TIZ与NMRAL1之间的相互作用，为NTZ的抗病毒机制提供了分子基础。

综上所述，NTZ对抗PRRSV显示出巨大潜力，并为我们理解其有效的抗病毒机制提供了深入的见解，为PRRSV的药物开发和治疗策略提供了重要的科学依据。

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.