The Great Deceiver: miR-2392's Hidden Role in Driving SARS-CoV-2 Infection
Autor: | J Tyson, McDonald, Francisco Javier, 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, Schisler, Christopher E, Mason, Anushree, Chatterjee, Robert, Meller, Afshin, Beheshti |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male Proteomics Hamster Inflammation Disease antiviral therapeutic Biology Antiviral Agents Article Transcriptome Mice In vivo Cricetinae microRNA medicine Animals Humans Hypoxia Aged miRNA Regulation of gene expression Aged 80 and over SARS-CoV-2 miR-2392 Ferrets COVID-19 Middle Aged In vitro Healthy Volunteers Rats COVID-19 Drug Treatment MicroRNAs nanoligomers Gene Expression Regulation ROC Curve Cancer research biomarker Female medicine.symptom Glycolysis Biomarkers |
Zdroj: | Cell Reports bioRxiv |
Popis: | 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. Graphical abstract McDonald et al. uncover a role of a circulating microRNA, miR-2392, as a potential biomarker for COVID-19 and begin development of a potential COVID-19 therapeutic and antiviral to inhibit miR-2392. |
Databáze: | OpenAIRE |
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