Role of miR-2392 in driving SARS-CoV-2 infection

• DOI: 10.1016/j.celrep.2021.109839
• Publication Date: 2021-09-30T04:34:14Z
• Authors: J. Tyson McDonald; Francisco J. 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-Bu...; 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 Da...; 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-V...; Charles Vanderburg; Douglas C. Wallace; Jonathan C. Schisler; Christopher E. Mason; Anushree Chatterjee; Robert Meller; Afshin Beheshti; Shannon M. Wallet; Robert Maile; Matthew C. Wolfgang; Robert S. Hagan; Jason R. Mock; Natalie M. Bowman; Jose L. Torres-Ca...; Miriya K. Love; Suzanne L. Meinig; Will Lovell; Colleen Rice; Olivia Mitchem; Dominique Burgess; Jessica Suggs; Jordan Jacobs
• Keywords: Adult; Male; QH301-705.5; antiviral therapeutic; Antiviral Agents; Article; Mice; Cricetinae; Animals; Humans; Biology (General); Hypoxia; miRNA; Aged; Aged, 80 and over; Inflammation; microRNA; SARS-CoV-2; miR-2392; Ferrets; COVID-19; Middle Aged; Healthy Volunteers; 3. Good health; MicroRNAs; nanoligomers; Gene Expression Regulation; biomarker; Female; Glycolysis; Biomarkers

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.