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Original Research ARTICLE

Front. Pharmacol. | doi: 10.3389/fphar.2020.582003

Pathways and microRNAs bioinformatics analyses identifying possible existing therapeutics for COVID-19 treatment Provisionally accepted The final, formatted version of the article will be published soon. Notify me

 Laura Teodori1,  Piero Sestili2, Valeria Madiai1, Sofia Coppari2, Daniele Fraternale2, Marco B. Rocchi2,  Seeram Ramakrishna3 and  Maria Cristina Albertini2*
  • 1Diagnostics and Metrology Laboratory, Frascati Science, Italy
  • 2University of Urbino Carlo Bo, Italy
  • 3National University of Singapore, Singapore

Over 240.000 SARS-COV-2 positive cases have been confirmed in Italy as June 2020, with the number of deaths exceeding 34 thousand, making Italy between major Countries for world COVID-19 deaths. Such enormous occurrence of infected and dead people raises the urgent demand of effective fast available treatments to control and diminish this pandemic. Discovering the cellular/molecular mechanisms of SARS-COV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and for therapeutically approaching it. From literature data, through a bioinformatics approach, an in silico analysis was performed, to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. We thus investigate on the signaling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets and functions. We predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with deacetylate histones pathway HDAC. Our results matched with the available clinical data. We hypothesize the current and EMA-approved, SARS-COV-2 off-label, HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. A ranked list of compounds is given that can be tested.

Keywords: COVID-19, SARS-CoV-2, HDAC, Hypertension, ACE2

Received: 20 Jul 2020; Accepted: 02 Oct 2020.

Copyright: © 2020 Teodori, Sestili, Madiai, Coppari, Fraternale, Rocchi, Ramakrishna and Albertini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Maria Cristina Albertini, University of Urbino Carlo Bo, Urbino, 61029, Marche, Italy, maria.albertini@uniurb.it