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

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

  • Bioorg Chem. 2020 May;98:103733. doi: 10.1016/j.bioorg.2020.103733.
Andraž Lamut 1 Marina Gjorgjieva 1 Lieve Naesens 2 Sandra Liekens 2 Katja-Emilia Lillsunde 3 Päivi Tammela 3 Danijel Kikelj 1 Tihomir Tomašič 4
Affiliations

Affiliations

  • 1 University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
  • 2 Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
  • 3 Drug Research Programme, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5EFI-00014, Finland.
  • 4 University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia. Electronic address: tihomir.tomasic@ffa.uni-lj.si.
Abstract

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 EC50 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.

Keywords

Antiviral agent; Benzo[d]thiazole; Hsp90; Influenza virus.

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