Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis.

In addition to uncontrolled diabetes and the excess use of corticosteroids, it is believed that other factors may be responsible for the recent spurt of COVID-19 associated mucormycosis (CAM). In the present paper it is argued that COVID-19 increases the susceptibility of the patients to mucormycosis by augmenting the virulence factors of the mucor species, where deficient synthesis of melatonin plays a key role. Melatonin is synthesized from tryptophan via the serotonin pathway and melatonin deficiency in COVID-19 arises from the faulty absorption of tryptophan from the food because SARS-CoV-2 downregulates angiotensin-converting enzyme-2, the chaperone of the transporter of tryptophan. The enhanced fungal virulence in COVID-19 can be mitigated by correcting the melatonin deficiency as melatonin can prevent iron acquisition of the mucor species and inhibit their morphological transition from the yeast to the virulent hyphal form, given the fact that melatonin is an iron chelator, calmodulin blocker and inhibitor of myeloperoxidase as well as inhibitor of ferroptosis and pyroptosis. Also, by lowering the expression of glucose-regulated protein 78 and by inhibiting the suppression of T-cell immunity, melatonin can further increase the resistance of the patients to mucormycosis. Accordingly, clinical trials should be carried out on tryptophan supplementation, administration of selective serotonin reuptake inhibitors (to increase serotonin, the precursor of melatonin), and exogenous melatonin to find out how they perform in eliminating or reducing the propensity of the coronavirus patients to CAM.