*4.5. Two Calcineurin Inhibitors in Clinical Use*

Currently, cyclosporin A (CsA) and tacrolimus (FK506) are CNIs used in the clinical setting. CsA was approved by the FDA in 1983. It is a cyclic polypeptide, derived from the fungus

*Tolypocladium inflatum* [43]. Tacrolimus (also known as FK506), used since 1995, is a macrolide antibiotic, isolated from the soil bacterium *Streptomyces tsukabensis*, with quite a similar mechanism of action as CsA [44], which will be discussed later.

**Figure 1.** Pathogenesis of COVID-19 and the suggested actions of cyclosporin and tacrolimus. Upon binding of a CoV protein to cyclophilins, the Calcineurin/nuclear factor of activated T cells (NF-AT) pathway is activated, via the coronaviral non-structural protein-1 (Nsp) leading to a systemic cytokine storm. In addition, cyclophilin A (CypA) probably stimulates CoV replication. Cyclosporin A inhibits viral replication. Adapted from Tanaka et al., *Viruses* **2013**, *5*, 1250–1260; doi:10.3390/v5051250.
