Role of miR-2392 in driving SARS-CoV-2 infection
2021
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-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 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-Castillo | Miriya K. Love | Suzanne L. Meinig | Will Lovell | Colleen Rice | Olivia Mitchem | Dominique Burgess | Jessica Suggs | Jordan Jacobs
Summary: 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.
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