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
Rok vydání: 2021
Předmět:
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