The Great Deceiver: miR-2392's Hidden Role in Driving SARS-CoV-2 Infection
McDonald, J. T.; Enguita, F. J.; Taylor, D.; Griffin, R. J.; Priebe, W.; Emmett, M. R.; Sajadi, M.; Harris, A. D.; Clement, J.; Dybas, J. M.; Aykin-Burns, N.; Guarnieri, J. W.; Singh, L. N.; Grabham, P.; Baylin, S.; Yousey, A.; Pearson, A. N.; Corry, P. M.; Saravia-Butler, A.; Aunins, T. R.; Sharma, S.; Nagpal, P.; Meydan, C.; Foox, J.; Mozsary, C.; Cerqueira, B.; Zaksas, V.; Singh, U.; Wurtele, E. S.; Costes, S. V.; Davanzo, G. G.; Galeano, D.; Paccanaro, A.; Meinig, S. L.; Hagan, R. S.; Bowman, N. M.; UNC COVID-19 Pathobiology Consortium, ; Wolfgang, M. C.; Altinok, S.; Sapoval, N.; Treange
Show abstract
MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with 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 COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of COVID-19 positive patients, but not detected in COVID-19 negative patients. These findings indicate the potential for developing a novel, minimally invasive, COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we have developed a novel 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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