# Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses

## 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.

## Key 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 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.