Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers

Abstract

The pandemic dissemination of the SARS-CoV-2 led, on the one hand, to a worldwide effort to develop mechanistic-based therapeutics and vaccines, and on the other hand, the searching for determining the spreaders and the mechanisms of transmission. Melatonin, a multitask molecule, orchestrates defense responses by allowing the proper mounting, duration, and magnitude of innate immune responses. Melatonin is synthesized on demand by immune-competent cells and constitutively by resident macrophages such as alveolar macrophages. Here we investigated whether the expression of genes relevant to virus invasion and infection varies according to a genic index (MEL-Index) that estimates the capacity of the lung to synthesize melatonin. A COVID-19-Signature composed of 455 genes of 288 human lungs (GTEX, UCSD) was correlated with MEL-Index by Pearson correlation test, gene-set enrichment analysis, and networking tool that integrates the connectivity between the most expressed genes, allowing us to compare the same set of genes under different states. The three independent procedures point to a negative relationship between MEL-Index and SARS-CoV-2 infection. The entry in epithelial AT2 cells should be hampered by a positive correlation TMRPSS2 and a negative correlation with the coding gene for furin, suggesting dysfunctional processing in virus spike. Moreover, MEL-Index also negatively correlates with the genes that codify the proteins of multi-molecular receptor complex CD147, the gateway in macrophages, and other immune cells. In summary, the perspective that lung and respiratory tract melatonin could be a natural protective factor opens new epidemiological and pharmacological perspectives, as high MEL-Index scores could be predictive of asymptomatic carriers, and nasal administrated melatonin could prevent evolution of presymptomatic carriers.

Melatonergic index as a prognostic biomarker of reproductive organ cancers: correlations with metabolic parameters as well as clock genes PER1 and TIMELESS

“…The knowledge of a melatonergic system based-tumor algorithm helps to guide evaluations of prognosis and disease progression. The two-gene signature model (ASMT:CYPs isoforms) has been systematically applied in the context of carcinogenesis and infectious diseases to identify high-from low-risk patients (19,20,35). Specifically, for reproductive organ tumors, we provided three melatonergic indices (1-3) which can be used to compose low or even negative values according to melatonin synthesis and metabolism by CYPs (CYP1A1, CYP1A2, and CYP1B1).…”

Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies

“…It is the daily pattern of melatonin secretion that carries information for circadian and seasonal temporal organization (32). Melatonin is also synthesized by the skin, guts, and lungs in a constitutive manner, and on-demand by activated immune-competent cells, such as monocyte-derived and resident macrophages, microglia and lymphocytes (1,33,34).…”

Covid 19: Diet Composition and Health

“…Melatonin produced in the lungs can be helpful for fighting SARS-CoV-2. It not only has strong preventive properties, but also inhibits the spread of the coronavirus in the body, according to the findings of researchers from the University of São Paulo (USP) [ 127 ]. Experts suggest that it could be used to produce a drug to treat COVID-19.…”