Role of miR-2392 in driving SARS-CoV-2 infection
J. Tyson McDonald, Francisco J. Enguita, Deanne Taylor, Robert J. Griffin, Waldemar Priebe, Mark R. Emmett, Mohammad M. Sajadi, Anthony D. Harris, Jean Clement, Joseph M. Dybas, Nükhet Aykin‐Burns, Joseph W. Guarnieri, Larry N. Singh, Peter Grabham, Stephen B. Baylin, Aliza Yousey, Andrea Pearson, Peter M. Corry, Amanda Saravia-Butler, Thomas R. Aunins, Sadhana Sharma, Prashant Nagpal, Cem Meydan, Jonathan Foox, Christopher Mozsary, Bianca Cerqueira, Victoria 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, Shannon M. Wallet, Robert Maile, Matthew C. Wolfgang, Robert S. Hagan, Jason R. Mock, Natalie M. Bowman, Jose Torres‐Castillo, Miriya K. Love, Suzanne L. Meinig, W. George Lovell, Colleen Rice, Olivia Mitchem, Dominique Burgess, Jessica Suggs, Jordan Jacobs, Matthew C. Wolfgang, Selin Altınok, Nicolae Sapoval, Todd J. Treangen, Pedro M. Moraes‐Vieira, Charles Vanderburg, Douglas C. Wallace, Jonathan C. Schisler, Christopher E. Mason, Anushree Chatterjee, Robert Meller, Afshin Beheshti
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (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 coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a 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.