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

Jackie McDonald; Francisco J. Enguita; Deanne M. Taylor; Robert J. Griffin; Waldemar Priebe; Mark R. Emmett; Mohammad M. Sajadi; Anthony D. Harris; Jean Clement; Joseph M. Dybas; Nükhet Aykin‐Burns; Joseph W. Guarnieri; Larry N. Singh; Peter W. 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; Victoria Zaksas; Urminder Singh; Eve Syrkin Wurtele; Sylvain V. Costes

doi:10.1101/2021.04.23.441024

Systems BiologybioRxivApr 23, 2021

Preprint

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

Jackie McDonald iD, Francisco J. Enguita iD, Deanne M. Taylor iD, Robert J. Griffin iD, Waldemar Priebe iD, Mark R. Emmett iD, Mohammad M. Sajadi iD, Anthony D. Harris iD, Jean Clement, Joseph M. Dybas iD, Nükhet Aykin‐Burns iD, Joseph W. Guarnieri iD, Larry N. Singh iD, Peter W. Grabham iD, Stephen B. Baylin iD, Aliza Yousey, Andrea N Pearson, Peter M. Corry iD, Amanda Saravia-Butler iD, Thomas R. Aunins iD, Sadhana Sharma iD, Prashant Nagpal iD, Cem Meydan iD, Jonathan Foox iD, Christopher Mozsary iD, , Afshin Beheshti iD

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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