The Great Deceiver: miR-2392's Hidden Role in Driving SARS-CoV-2 Infection

 J. Tyson McDonald, Francisco Javier Enguita, Deanne Taylor, Richard A Bowen, Robert J Griffin, Waldemar Priebe, Mark R Emmett, Marisa McGrath, Mohammad Sajadi, Anthony D Harris, Jean Clement, Joseph M Dybas, Nukhet Aykin-Burns, Joseph W Guarnieri,  

View ORCID ProfileLarry N Singh, Peter Grabham, Stephen Baylin, Aliza Yousey, Andrea N Pearson, Peter M Corry, Amanda Saravia-Butler, Thomas R Aunins, Prashant Nagpal, Cem Meydan, Jonathan Foox, Christopher Mozsary, Bianca Cerqueira, Viktorija Zaksas,  View ORCID ProfileUrminder Singh,  View ORCID ProfileEve Syrkin Wurtele,  View ORCID ProfileSylvain V Costes, Diego Galeano, Alberto Paccanaro, Suzanne L Meinig, Robert S Hagan, Natalie M Bowman, UNC COVID-19 Pathobiology Consortium,  View ORCID ProfileMatthew C Wolfgang,  View ORCID ProfileSelin Altinok, Nicolae Sapoval,  View ORCID ProfileTodd J Treangen, Matthew Frieman,  View ORCID ProfileCharles Vanderburg,  View ORCID ProfileJonathan C Schisler,  View ORCID ProfileChristopher Mason, Anushree Chatterjee,  View ORCID ProfileRobert Meller,  View ORCID ProfileAfshin Beheshti

doi: https://doi.org/10.1101/2021.04.23.441024

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.04.23.441024v1.full.pdf

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we found that miR-2392 was key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of COVID-19 patients tested, but not detected in COVID-19 negative patients. These findings indicate the potential for developing a novel, minimally invasive, COVID-19 detection method. Lastly, using both in vitro human and in vivo hamster models, we have developed a novel miRNA-based antiviral therapeutic targeting miR-2392 that significantly reduces SARS-CoV-2 viability and may potentially inhibit a COVID-19 disease state in the host.

Competing Interest Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2021.04.23.441024v1