A2 Refereed review article in a scientific journal
Therapeutic targeting of HSP90 in herpesvirus infections, past and future challenges
Authors: Chakraborty, Abir; Roos-Mattjus, Pia; Gramolelli, Silvia
Publisher: Informa UK Limited
Publication year: 2025
Journal: Transactions of the Royal Society of South Africa
Journal name in source: Transactions of the Royal Society of South Africa
Volume: 80
Issue: 1
First page : 47
Last page: 52
ISSN: 0035-919X
eISSN: 2154-0098
DOI: https://doi.org/10.1080/0035919X.2025.2473552
Web address : https://doi.org/10.1080/0035919x.2025.2473552
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/499583660
Eukaryotic cells rely on a highly conserved chaperone machinery to maintain protein homeostasis (proteostasis). The activity of the HSP90 chaperone is critical for the appropriate folding and stability of a wide range of substrate proteins (client proteins) involved in fundamental cellular functions. Despite its abundance, HSP90 levels increase during pathological conditions such as cancer and viral infections, leading to cellular dependence on its activity. Hence, the inhibition of HSP90 has emerged as a potential therapeutic avenue, which has been explored particularly in cancer, antiplasmodial and antiviral treatments. This review provides a general overview of the structure and functions of HSP90, the main inhibitors that have been developed and the outcome, as well as HSP90 involvement in different herpesvirus infections. Compelling evidence identifies HSP90 as a promising pan-herpesviral target. Notably HSP90 inhibitors could outperform other antivirals as they do not promote the insurgence of resistant viral strains. Regardless, there are still great challenges ahead towards the development of safe and efficacious HSP90 inhibitors. New research should still pursue this avenue and aim to develop more selective and less toxic compounds.
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Funding information in the publication:
This work was supported by Finnish Cultural Foundation; Åbo Akademi University; Swedish Cultural Foundation in Finland; The Finnish Society for Sciences and Letters; Research Council of Finland.
