4.8 Article

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

Journal

CELL REPORTS
Volume 37, Issue 3, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.109839

Keywords

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Categories

Funding

  1. Translational Research Institute of Space Health through NASA [T-0404]
  2. KBR, Inc.
  3. NASA High-End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center
  4. DOD [W81XWH-21-1-0128]
  5. NIGMS [P20 GM1009005]
  6. Individual National Research Service [F32-AI147587]
  7. NIH/NHBLI [K08 HL143271, NIH/NHLBI R03 HL155249]
  8. NIH/NCI [U54 CA260543, NSF 1956233]
  9. Biotechnology and Biological Sciences Research Council [BB/K004131/1, BB/F00964X/1, BB/M025047/1]
  10. Consejo Nacional de Ciencia y Tecnologia Paraguay (CONACyT) [14-INV-088andPINV15-315, 1660648]
  11. NSF IOS [1546858]
  12. CONACYT [PINV20-337]
  13. Fundacao Getulio Vargas
  14. National Center for Advancing Translational Sciences (NCATS)
  15. NIH [UL1TR002489, 2KR1272005, 550KR242003]
  16. Fundo de Apoio ao Ensino, Pesquisa e Extensao (FAEPEX) [2274/20]
  17. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brazil (CAPES) [001, A549 SARS-CoV-2]
  18. Division Of Integrative Organismal Systems
  19. Direct For Biological Sciences [1546858] Funding Source: National Science Foundation

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The research demonstrates that miR-2392 is associated with SARS-CoV-2 infection, with potential for use in COVID-19 detection and as a target for antiviral therapy. Targeting miR-2392 can significantly reduce SARS-CoV-2 viability, indicating a potential treatment for COVID-19.
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 circulatingmiRNA, 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 aminimally invasive COVID-19 detectionmethod. 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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