Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses
Elisa Feyles, Tommaso Felicetti, Irene Arduino, Massimo Rittà, Andrea Civra, Luisa Muratori, Stefania Raimondo, David Lembo, Giuseppe Manfroni, Manuela Donalisio
TL;DR
Researchers found a compound that can inhibit multiple respiratory viruses, including RSV, HCoV, and influenza, with potential for developing a broad-spectrum antiviral treatment.
Contribution
A new broad-spectrum antiviral compound with low micromolar efficacy and cell-independent activity was identified from PBTZ analogues.
Findings
The compound inhibits multiple strains of RSV, HCoV, and IFV with EC50 values in the low micromolar range.
It shows antiviral activity and cytocompatibility in a 3D bronchial epithelium model resembling in vivo conditions.
The compound localizes in the cytosol and inhibits replicative phases in a virus-specific manner.
Abstract
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 in a virus-specific manner. Overall, the selected PBTZ represents a good starting point for further…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 22
Figure 23
Figure 24
Figure 25
Figure 26
Figure 27
Figure 28
Figure 29
Figure 30
Figure 31
Figure 32
Figure 33Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsRespiratory viral infections research · interferon and immune responses · Influenza Virus Research Studies