The Great Deceiver: miR-2392's Hidden Role in Driving SARS-CoV-2 Infection

McDonald, J. T.; Enguita, F. J.; Taylor, D.; Bowen, R. A.; Griffin, R. J.; Priebe, W.; Emmett, M. R.; McGrath, M.; 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.; Nagpal, P.; Meydan, C.; Foox, J.; Mozsary, C.; Cerqueira, B.; Zaksas, V.; Singh, U.; Wurtele, E. S.; Costes, S. V.; 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.; Treangen

doi:10.1101/2021.04.23.441024

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bioRxiv · 10.1101/2021.04.23.441024

The Great Deceiver: miR-2392's Hidden Role in Driving SARS-CoV-2 Infection

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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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McDonald, J. T., Enguita, F. J., Taylor, D., Bowen, R. A., Griffin, R. J., Priebe, W., Emmett, M. R., McGrath, M., 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., Nagpal, P., Meydan, C., Foox, J., Mozsary, C., Cerqueira, B., Zaksas, V., Singh, U., Wurtele, E. S., Costes, S. V., 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., Treangen. 2021-04-23. The Great Deceiver: miR-2392's Hidden Role in Driving SARS-CoV-2 Infection. https://doi.org/10.1101/2021.04.23.441024

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