Anti-influenza virus activity of benzo[d]thiazoles that target heat shock protein 90

• A series of benzo[ d ]thiazoles was tested for anti-influenza virus activity. • Compounds 1 and 4 showed low µM EC 50 values against influenza A and B viruses. • Compounds 1 and 4 displayed submicromolar binding affinities for Hsp90β. • Hsp90 inhibition is a plausible mechanism for anti-influenza activity of compounds. Seasonal or pandemic influenza virus infections are a worldwide health problem requiring antiviral therapy. Since virus resistance to the established neuraminidase inhibitors and novel polymerase inhibitors is growing, new drug targets are needed. Heat shock protein 90 (Hsp90) is associated with several aspects of the influenza virus life cycle, and is considered a relevant host cell target. We report here on a series of benzo[ d ]thiazole and 4,5,6,7-tetrahydrobenzo[ d ]thiazole derivatives with robust and selective activities against influenza A (H1N1, H3N2) and influenza B viruses. Two compounds, 1 and 4 , have low micromolar EC 50 values and show high binding affinities for Hsp90, which suggests that inhibition of Hsp90 is the mechanism underlying their antiviral effects. These compounds represent suitable scaffolds for designing novel Hsp90 inhibitors with favourable activities against influenza virus.