Role of miR-2392 in driving SARS-CoV-2 infection

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  • McDonald, J.T.
    • Other Affiliation: Georgetown University School of Medicine
  • Enguita, F.J.
    • Other Affiliation: Universidade de Lisboa
  • Taylor, D.
    • Other Affiliation: University of Pennsylvania
  • Griffin, R.J.
    • Other Affiliation: University of Arkansas for Medical Sciences
  • Priebe, W.
    • Other Affiliation: University of Texas MD Anderson Cancer Center
  • Emmett, M.R.
    • Other Affiliation: University of Texas Medical Branch
  • Sajadi, M.M.
    • Other Affiliation: University of Maryland School of Medicine
  • Harris, A.D.
    • Other Affiliation: University of Maryland School of Medicine
  • Clement, J.
    • Other Affiliation: University of Maryland School of Medicine
  • Dybas, J.M.
    • Other Affiliation: The Children's Hospital of Philadelphia
  • Aykin-Burns, N.
    • Other Affiliation: University of Pennsylvania
  • Guarnieri, J.W.
    • Other Affiliation: The Children's Hospital of Philadelphia
  • Singh, L.N.
    • Other Affiliation: The Children's Hospital of Philadelphia
  • Grabham, P.
    • Other Affiliation: Columbia University
  • Baylin, S.B.
    • Other Affiliation: Johns Hopkins School of Medicine
  • Yousey, A.
    • Other Affiliation: Morehouse School of Medicine
  • Pearson, A.N.
    • Other Affiliation: Morehouse School of Medicine
  • Corry, P.M.
    • Other Affiliation: University of Arkansas for Medical Sciences
  • Saravia-Butler, A.
    • Other Affiliation: NASA Ames Research Center
  • Aunins, T.R.
    • Other Affiliation: University of Colorado Boulder
  • Sharma, S.
    • Other Affiliation: University of Colorado Boulder
  • Nagpal, P.
    • Other Affiliation: Sachi Bioworks Inc.
  • Meydan, C.
    • Other Affiliation: Weill Cornell Medicine
  • Foox, J.
    • Other Affiliation: Weill Cornell Medicine
  • Mozsary, C.
    • Other Affiliation: Weill Cornell Medicine
  • Cerqueira, B.
    • Other Affiliation: United States Air Force School of Aerospace Medicine
  • Zaksas, V.
    • Other Affiliation: University of Chicago
  • Singh, U.
    • Other Affiliation: Iowa State University
  • Wurtele, E.S.
    • Other Affiliation: Iowa State University
  • Costes, S.V.
    • Other Affiliation: NASA Ames Research Center
  • Davanzo, G.G.
    • Other Affiliation: University of Campinas
  • Galeano, D.
    • Other Affiliation: National University of Asuncion
  • Paccanaro, A.
    • Other Affiliation: University of London
  • Meinig, S.L.
    • Affiliation: University of North Carolina at Chapel Hill
  • Hagan, R.S.
    • Affiliation: University of North Carolina at Chapel Hill
  • Bowman, N.M.
    • Affiliation: University of North Carolina at Chapel Hill
  • UNC COVID-19 Pathobiology Consortium
  • Wolfgang, M.C.
    • Affiliation: University of North Carolina at Chapel Hill
  • Altinok, S.
    • Affiliation: University of North Carolina at Chapel Hill
  • Sapoval, N.
    • Other Affiliation: Rice University
  • Treangen, T.J.
    • Other Affiliation: Rice University
  • Moraes-Vieira, P.M.
    • Other Affiliation: University of Campinas
  • Vanderburg, C.
    • Other Affiliation: Broad Institute of MIT and Harvard
  • Wallace, D.C.
    • Other Affiliation: The Children's Hospital of Philadelphia
  • Schisler, J.C.
    • Affiliation: University of North Carolina at Chapel Hill
  • Mason, C.E.
    • Other Affiliation: Weill Cornell Medicine
  • Chatterjee, A.
    • Other Affiliation: University of Colorado Boulder
  • Meller, R.
    • Other Affiliation: Morehouse School of Medicine
  • Beheshti, A.
    • Other Affiliation: NASA Ames Research Center
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.
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  • Article
Rights statement
  • In Copyright
License
  • Attribution-NonCommercial-NoDerivs 3.0 United States
Journal title
  • Cell Reports
Journal volume
  • 37
Journal issue
  • 3
Language
  • English
Version
  • Publisher
ISSN
  • 2211-1247

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