PDF(Pubmed)
Abstract：
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a potentially severe respiratory disease, the coronavirus disease 2019 (COVID-19), an ongoing pandemic with limited therapeutic options. Here, we assessed the anti-coronavirus activity of synthetic RNAs mimicking specific domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs). These molecules are known to exert broad-spectrum antiviral activity in cell culture, mice and pigs effectively triggering the host innate immune response. The ncRNAs showed potent antiviral activity against SARS-CoV-2 after transfection in human intestinal Caco-2 and lung epithelium Calu-3 2B4 cells. When the in vivo efficacy of the FMDV ncRNAs was assessed in K18-hACE2 mice, administration of naked ncRNA before intranasal SARS-CoV-2 infection significantly decreased the viral load and the levels of pro-inflammatory cytokines in the lungs compared with untreated infected mice. The ncRNAs were also highly efficacious when assayed against common human HCoV-229E and porcine transmissible gastroenteritis virus (TGEV) in hepatocyte-derived Huh-7 and swine testis ST cells, respectively. These results are a proof of concept of the pan-coronavirus antiviral activity of the FMDV ncRNAs including human and animal divergent coronaviruses and potentially enhance our ability to fight future emerging variants.
摘要：
严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）是潜在严重呼吸系统疾病的病原体，2019年冠状病毒病（COVID-19），持续的大流行，治疗选择有限。这里,我们评估了模拟口蹄疫病毒(FMDV)基因组(ncRNA)非编码区特定结构域的合成RNA的抗冠状病毒活性.已知这些分子在细胞培养中发挥广谱抗病毒活性,小鼠和猪有效触发宿主的先天免疫应答。在人肠道Caco-2和肺上皮Calu-32B4细胞中转染后，ncRNA显示出对SARS-CoV-2的有效抗病毒活性。当在K18-hACE2小鼠中评估FMDVncRNAs的体内功效时，与未经治疗的感染小鼠相比，鼻内感染SARS-CoV-2之前施用裸ncRNA显着降低了肺部的病毒载量和促炎细胞因子水平。当在肝细胞来源的Huh-7和猪睾丸ST细胞中检测针对普通人类HCoV-229E和猪传染性胃肠炎病毒（TGEV）时，ncRNA也是高度有效的。分别。这些结果证明了FMDVncRNAs的泛冠状病毒抗病毒活性的概念，包括人类和动物不同的冠状病毒，并可能增强我们对抗未来新兴变体的能力。
