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 literatures 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 investigation and experimentation into the calcineurin complex are strongly required. This review 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.