Cell Reports (Oct 2021)
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,
- 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,
- Matthew C. Wolfgang,
- Selin Altinok,
- 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,
- Shannon M. Wallet,
- Robert Maile,
- Matthew C. Wolfgang,
- Robert S. Hagan,
- Jason R. Mock,
- Natalie M. Bowman,
- Jose L. Torres-Castillo,
- Miriya K. Love,
- Suzanne L. Meinig,
- Will Lovell,
- Colleen Rice,
- Olivia Mitchem,
- Dominique Burgess,
- Jessica Suggs,
- Jordan Jacobs
Affiliations
- J. Tyson McDonald
- COVID-19 International Research Team; Georgetown University School of Medicine, Washington, DC 20007, USA
- Francisco J. Enguita
- COVID-19 International Research Team; Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal
- Deanne Taylor
- COVID-19 International Research Team; The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; University of Pennsylvania, Philadelphia, PA 19104, USA
- Robert J. Griffin
- COVID-19 International Research Team; University of Arkansas for Medical Sciences, Little Rock, AK 72211, USA
- Waldemar Priebe
- COVID-19 International Research Team; University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Mark R. Emmett
- COVID-19 International Research Team; University of Texas Medical Branch, Galveston, TX 77555, USA
- Mohammad M. Sajadi
- University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Anthony D. Harris
- University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Jean Clement
- University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Joseph M. Dybas
- COVID-19 International Research Team; The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
- Nukhet Aykin-Burns
- University of Pennsylvania, Philadelphia, PA 19104, USA
- Joseph W. Guarnieri
- COVID-19 International Research Team; The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
- Larry N. Singh
- COVID-19 International Research Team; The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
- Peter Grabham
- COVID-19 International Research Team; Columbia University, New York, NY 10032, USA
- Stephen B. Baylin
- COVID-19 International Research Team; Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
- Aliza Yousey
- COVID-19 International Research Team; Morehouse School of Medicine, Atlanta, GA 30310, USA
- Andrea N. Pearson
- Morehouse School of Medicine, Atlanta, GA 30310, USA
- Peter M. Corry
- COVID-19 International Research Team; University of Arkansas for Medical Sciences, Little Rock, AK 72211, USA
- Amanda Saravia-Butler
- COVID-19 International Research Team; Logyx LLC, Mountain View, CA 94043, USA; NASA Ames Research Center, Moffett Field, CA 94035, USA
- Thomas R. Aunins
- University of Colorado Boulder, Boulder, CO 80303, USA
- Sadhana Sharma
- University of Colorado Boulder, Boulder, CO 80303, USA; Sachi Bioworks Inc., Boulder, CO 80301, USA
- Prashant Nagpal
- Sachi Bioworks Inc., Boulder, CO 80301, USA; Antimicrobial Regeneration Consortium, Boulder Labs, Boulder, CO 80301, USA; Quantum Biology Inc., Boulder, CO 80301, USA
- Cem Meydan
- Weill Cornell Medicine, New York, NY 10065, USA
- Jonathan Foox
- Weill Cornell Medicine, New York, NY 10065, USA
- Christopher Mozsary
- Weill Cornell Medicine, New York, NY 10065, USA
- Bianca Cerqueira
- COVID-19 International Research Team; KBR Space & Science, San Antonio, TX 78235, USA; United States Air Force School of Aerospace Medicine, Lackland AFB, San Antonio, TX 78236, USA
- Viktorija Zaksas
- COVID-19 International Research Team; University of Chicago, Chicago, IL 60615, USA
- Urminder Singh
- COVID-19 International Research Team; Iowa State University, Ames, IA 50011, USA
- Eve Syrkin Wurtele
- COVID-19 International Research Team; Iowa State University, Ames, IA 50011, USA
- Sylvain V. Costes
- NASA Ames Research Center, Moffett Field, CA 94035, USA
- Gustavo Gastão Davanzo
- University of Campinas, Sao Paulo, Brazil
- Diego Galeano
- COVID-19 International Research Team; Fundação Getulio Vargas, Rio de Janeiro, Brazil; National University of Asuncion, San Lorenzo, Central, Paraguay
- Alberto Paccanaro
- COVID-19 International Research Team; Fundação Getulio Vargas, Rio de Janeiro, Brazil; University of London, Egham Hill, Egham, UK
- Suzanne L. Meinig
- University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Robert S. Hagan
- University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Natalie M. Bowman
- University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Matthew C. Wolfgang
- University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Selin Altinok
- University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Nicolae Sapoval
- Rice University, Houston, TX 77005, USA
- Todd J. Treangen
- Rice University, Houston, TX 77005, USA
- Pedro M. Moraes-Vieira
- COVID-19 International Research Team; University of Campinas, Sao Paulo, Brazil
- Charles Vanderburg
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Douglas C. Wallace
- COVID-19 International Research Team; The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; University of Pennsylvania, Philadelphia, PA 19104, USA
- Jonathan C. Schisler
- COVID-19 International Research Team; University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Christopher E. Mason
- COVID-19 International Research Team; Weill Cornell Medicine, New York, NY 10065, USA; New York Genome Center, New York, NY, USA
- Anushree Chatterjee
- COVID-19 International Research Team; University of Colorado Boulder, Boulder, CO 80303, USA; Sachi Bioworks Inc., Boulder, CO 80301, USA; Antimicrobial Regeneration Consortium, Boulder Labs, Boulder, CO 80301, USA
- Robert Meller
- COVID-19 International Research Team; Morehouse School of Medicine, Atlanta, GA 30310, USA
- Afshin Beheshti
- COVID-19 International Research Team; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; KBR, NASA Ames Research Center, Moffett Field, CA 94035, USA; Corresponding author
- Shannon M. Wallet
- Robert Maile
- Matthew C. Wolfgang
- Robert S. Hagan
- Jason R. Mock
- Natalie M. Bowman
- Jose L. Torres-Castillo
- Miriya K. Love
- Suzanne L. Meinig
- Will Lovell
- Colleen Rice
- Olivia Mitchem
- Dominique Burgess
- Jessica Suggs
- Jordan Jacobs
- Journal volume & issue
-
Vol. 37,
no. 3
p. 109839
Abstract
Summary: 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.
