Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis
Open Access
- 25 September 2020
- journal article
- research article
- Published by MDPI AG in Brain Sciences
- Vol. 10 (10), 666
- https://doi.org/10.3390/brainsci10100666
Abstract
Background: Neuroinvasion of severe acute respiratory syndrome coronavirus (SARS-CoV) is well documented and, given the similarities between this virus and SARS-CoV-2, it seems that the neurological impairment that is associated with coronavirus disease 2019 (COVID-19) is due to SARS-CoV-2 neuroinvasion. Hypothalamic circuits are exposed to the entry of the virus via the olfactory bulb and interact centrally with crucial respiratory nuclei. Hypothalamic microRNAs are considered as potential biomarkers and modulators for various diseases and future therapeutic targets. The present study aims to investigate the microRNAs that regulate the expression of hypothalamic angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential elements for SARS-CoV-2 cell entry. Methods: To determine potential hypothalamic miRNAs that can directly bind to ACE2 and TMPRSS2, multiple target bioinformatics prediction algorithms were used, including miRBase, Target scan, and miRWalk2.029. Results: Our in silico analysis has revealed that, although there are over 5000 hypothalamic miRNAs, around 31 miRNAs and 29 miRNAs have shown binding sites and strong binding capacity against ACE2 and TMPRSS2, respectively. Conclusion: These novel potential hypothalamic miRNAs can be used to identify new therapeutic targets to treat neurological symptoms in COVID-19 patients via regulation of ACE2 and TMPRSS2 expression.Keywords
This publication has 71 references indexed in Scilit:
- Differentially Expressed miRNAs after GnRH Treatment and Their Potential Roles in FSH Regulation in Porcine Anterior Pituitary CellPLOS ONE, 2013
- Genome Regulation by Long Noncoding RNAsAnnual Review of Biochemistry, 2012
- Efficient Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by the Transmembrane Protease TMPRSS2Journal of Virology, 2010
- Proteolytic Activation of the 1918 Influenza Virus HemagglutininJournal of Virology, 2009
- The Vienna RNA WebsuiteNucleic Acids Research, 2008
- The androgen‐regulated type II serine protease TMPRSS2 is differentially expressed and mislocalized in prostate adenocarcinomaThe Journal of Pathology, 2008
- The evolution of gene regulation by transcription factors and microRNAsNature Reviews Genetics, 2007
- MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous systemGenome Biology, 2007
- miR-7b, a microRNA up-regulated in the hypothalamus after chronic hyperosmolar stimulation, inhibits Fos translationProceedings of the National Academy of Sciences of the United States of America, 2006
- Silencing SARS‐CoV Spike protein expression in cultured cells by RNA interferenceFEBS Letters, 2004