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

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 show that miR-2392 is 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 positive patients, 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 in vitro human and in vivo hamster models, we have developed a novel miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters and may potentially inhibit a COVID-19 disease state in humans.

• Authors: J Tyson McDonald, Francisco Javier Enguita, Deanne Taylor, Robert J Griffin, Waldemar Priebe, Mark R Emmett, Mohammad M Sajadi, Anthony D Harris, Jean Clement, Joseph M Dybas, Nukhet Aykin-Burns, Joseph W Guarnieri, Larry N Singh, Peter Grabham, Stephen B Baylin, Aliza Yousey, Andrea N Pearson, Peter M Corry, Amanda Saravia-Butler, Thomas R Aunins, Sadhana Sharma, Prashant Nagpal, Cem Meydan, Jonathan Foox, Christopher Mozsary, Bianca Cerqueira, Viktorija Zaksas, Urminder Singh, Eve Syrkin Wurtele, Sylvain V Costes, Gustavo Gastão Davanzo, Diego Galeano, Alberto Paccanaro, Suzanne L Meinig, Robert S Hagan, Natalie M Bowman, UNC COVID-19 Pathobiology Consortium, Matthew C Wolfgang, Selin Altinok, Nicolae Sapoval, Todd J Treangen, Pedro M Moraes-Vieira, Charles Vanderburg, Douglas C Wallace, Jonathan Schisler, Christopher E Mason, Anushree Chatterjee, Robert Meller, Afshin Beheshti
• Journal: bioRxiv : the preprint server for biology (bioRxiv) (Aug 18 2021) United States
• PMID: 33948587 (Publication Type: Preprint)