1. Role of miR-2392 in driving SARS-CoV-2 infection.
- Author
-
McDonald JT, Enguita FJ, Taylor D, Griffin RJ, Priebe W, Emmett MR, Sajadi MM, Harris AD, Clement J, Dybas JM, Aykin-Burns N, Guarnieri JW, Singh LN, Grabham P, Baylin SB, Yousey A, Pearson AN, Corry PM, Saravia-Butler A, Aunins TR, Sharma S, Nagpal P, Meydan C, Foox J, Mozsary C, Cerqueira B, Zaksas V, Singh U, Wurtele ES, Costes SV, Davanzo GG, Galeano D, Paccanaro A, Meinig SL, Hagan RS, Bowman NM, Wolfgang MC, Altinok S, Sapoval N, Treangen TJ, Moraes-Vieira PM, Vanderburg C, Wallace DC, Schisler JC, Mason CE, Chatterjee A, Meller R, and Beheshti A
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Antiviral Agents pharmacology, Biomarkers metabolism, Cricetinae, Female, Ferrets, Gene Expression Regulation, Glycolysis, Healthy Volunteers, Humans, Hypoxia, Inflammation, Male, Mice, Middle Aged, Proteomics methods, ROC Curve, Rats, COVID-19 Drug Treatment, COVID-19 genetics, COVID-19 immunology, MicroRNAs genetics, SARS-CoV-2 genetics
- 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., Competing Interests: Declaration of interests A.C., P.N., S.V.C., and A.B. have a provisional patent based on the antiviral discovery and design. A.C., P.N., and S.S. are part of the company (Sachi Bioworks Inc.) that has filed a patent on the Nanoligomer technology., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF