biostudies-literatureFeyles EMUR PNRR Extended Partnership Initiative on Emerging Infectious DiseasesIntesa Sanpaolo - Fondo di Beneficenza890https://www.ebi.ac.uk/biostudies/studies/S-EPMC12299477biostudies-literatureUnknown17(7)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 EC₅₀ 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 VirusesBroad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses.PMC12299477PE00000007, INF-ACTB/2022/0185Manfroni GCivra ARitta MLembo DFeyles EArduino IMuratori LFelicetti TRaimondo SDonalisio MfalseBroad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses.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 EC₅₀ 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 2025-01-01T00:00:00Z2025 Jun2025-08-24T03:05:39.835Z2025-08-24T03:05:39.835ZS-EPMC122994774073350810.3390/v17070890