Fig. 3

Summary of salient facets of coronavirus spike protein and human hepcidin biology. On the top left of the figure, three trimeric spike proteins are depicted on a segment of the viral membrane, two in a figurative style and the middle trimer in a more detailed domain-specific format. One palmitate is shown attached to the cytoplasmic tail of the spike proteins, as per Fig. 1c. Following the binding step to ACE2, a stylized viral fusion step is depicted based on refs. [120,121,122], where an early fusion scenario (as opposed to endocytosis) is envisioned. The assembly of new viral spike proteins is shown to be taking place in an ER-Golgi intermediate compartment. On the right half of the figure, various elements of hepcidin and iron biology are depicted, which could result in potential outcomes such as coagulopathy, ferroptosis and hyperferritinemia. In terms of hepcidin’s binding to ferroportin, two possible scenarios are depicted, whereby hepcidin could bind to the extracellular face of ferroportin or deeper inside the transmembrane cavity. Lastly, the geometric shapes for the spike and ACE2 proteins were adapted from ref. [119], for ferroportin from ref. [30], and for ferritin from ref. [29], all with permission from the publisher (Springer Nature)