Feyles Elisa, Felicetti Tommaso, Arduino Irene, Rittà Massimo, Civra Andrea, Muratori Luisa, Raimondo Stefania, Lembo David, Manfroni Giuseppe, Donalisio Manuela
Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy.
Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo, 1, 06123 Perugia, Italy.
Viruses. 2025 Jun 24;17(7):890. doi: 10.3390/v17070890.
Cell-based phenotypic screening of a privileged in-house library composed of pyridobenzothiazolone (PBTZ) analogues was conducted against representative viruses responsible for common respiratory tract infections in humans, i.e., respiratory syncytial virus (RSV), human coronavirus type OC43 (HCoV-OC43), and influenza virus type A (IFV-A). We identified a compound with broad-spectrum inhibitory activity against multiple strains of RSV, HCoV, and IFV, with EC values in the low micromolar range and cell-independent activity. Its antiviral activity and cytocompatibility were confirmed in a fully differentiated 3D model of the bronchial epithelium mimicking the in vivo setting. The hit compound enters cells and localizes homogeneously in the cytosol, inhibiting replicative phases in a virus-specific manner. Overall, the selected PBTZ represents a good starting point for further preclinical development as a broad-spectrum antiviral agent that could address the continuous threat of new emerging pathogens and the rising issue of antiviral resistance.
对由吡啶并苯并噻唑酮（PBTZ）类似物组成的内部特权文库进行了基于细胞的表型筛选，以对抗导致人类常见呼吸道感染的代表性病毒，即呼吸道合胞病毒（RSV）、人冠状病毒OC43型（HCoV-OC43）和甲型流感病毒（IFV-A）。我们鉴定出一种对多种RSV、HCoV和IFV毒株具有广谱抑制活性的化合物，其EC值在低微摩尔范围内且具有细胞非依赖性活性。在模拟体内环境的支气管上皮细胞完全分化的3D模型中证实了其抗病毒活性和细胞相容性。命中化合物进入细胞并均匀地定位于细胞质中，以病毒特异性方式抑制复制阶段。总体而言，所选的PBTZ作为一种广谱抗病毒剂，为进一步的临床前开发提供了一个良好的起点，该抗病毒剂可以应对新出现病原体的持续威胁和抗病毒耐药性不断上升的问题。
