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

Lung melatonin modulates SARS-CoV-2 infection

  • Pedro A Fernandes, PhD Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo http://orcid.org/0000-0002-4323-5614
  • Gabriela S Kinker, Ph.D. International Research Center, A.C. Camargo Cancer Center, São Paulo http://orcid.org/0000-0003-1676-442X
  • Bruno V Navarro Laboratory of Plant Physiological Ecology (LAFIECO), Department of Botany, Institute of Biosciences, University of São Paulo, São Paulo
  • Vinicius C Jardim, Ph.D. Department of Computer Science, Institute of Mathematics and Statistics, University of São Paulo, São Paulo, http://orcid.org/0000-0001-9289-4328
  • Edson D Ribeiro-Paz Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo, Brazil
  • Marlina O Córdoba-Moreno Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo
  • Débora Santos-Silva, M.Sc. Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo
  • Sandra M Muxel Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo
  • André Fujita, Ph.D. Department of Computer Science, Institute of Mathematics and Statistics, University of São Paulo, São Paulo http://orcid.org/0000-0002-7756-7051
  • Carolina Borsoi Moraes, Ph.D. Department of Pharmaceutical Sciences, Federal University of Sao Paulo
  • Helder I Nakaya, Ph.D. Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo http://orcid.org/0000-0001-5297-9108
  • Marcos S Buckeridge, Prof. Laboratory of Plant Physiological Ecology (LAFIECO), Department of Botany, Institute of Biosciences, University of São Paulo, São Paulo, Brazil http://orcid.org/0000-0002-5455-8136
  • Regina P Markus, Ph.D., Prof. Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo http://orcid.org/0000-0003-4606-6120
DOI: https://doi.org/10.32794/mr11250090
Keywords: SARS-CoV-2 transmission, lung melatonin, MEL-Index score, virus infection

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.


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Published
2021-01-03
How to Cite
[1]
Fernandes, P.A., Kinker, G.S., Navarro, B.V., Jardim, V.C., Ribeiro-Paz, E.D., Córdoba-Moreno, M.O., Santos-Silva, D., Muxel, S.M., Fujita, A., Moraes, C., Nakaya, H.I., Buckeridge, M.S. and Markus, R.P. 2021. Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers. Melatonin Research. 4, 1 (Jan. 2021), 189-205. DOI:https://doi.org/https://doi.org/10.32794/mr11250090.
Issue
Vol 4 No 1 (2021): Melatonin Research
Section
Research Articles
DOI
https://doi.org/10.32794/mr11250090
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