Fungal calcineurin complex as an antifungal target: From past to present to future

The serine/threonine phosphatase calcineurin complex has been considered a prospective target for developing novel drugs due to its importance in fungal growth, virulence, and stress responses in pathogenic fungi. Therefore, two well-known immunosuppressants, FK506 and cyclosporine A were successfully identified to inhibit calcineurin by combining with FK506-binding protein 12 and cyclophilin A, respectively. However, these drugs are immunosuppressive and may exhibit serious side effects. There is a growing number of lit-eratures reported on further exploring functions of the calcineurin complex as promising antifungal targets. In general, the majority of the calcineurin complex structures are conserved but some functions are species-specific. Nevertheless, there still have a lot of functional motifs in the calcineurin complex that are unexplored. Therefore, further inves-tigation and experimentation into the calcineurin complex are strongly required. This re-view not only has summarized previous findings but also explored bioinformatics analysis along with structural models of the calcineurin complex for finding fungal -specific regions as potential targets, laying the groundwork for future research into new therapeutics.(c) 2022 British Mycological Society. Published by Elsevier Ltd. All rights reserved.