tetano
Editor, Senior Moderator
Cell Rep
. 2021 Sep 30;109839.
doi: 10.1016/j.celrep.2021.109839. Online ahead of print.
Role of miR-2392 in driving SARS-CoV-2 infection
J Tyson McDonald[SUP] 1 [/SUP], Francisco J Enguita[SUP] 2 [/SUP], Deanne Taylor[SUP] 3 [/SUP], Robert J Griffin[SUP] 4 [/SUP], Waldemar Priebe[SUP] 5 [/SUP], Mark R Emmett[SUP] 6 [/SUP], Mohammad M Sajadi[SUP] 7 [/SUP], Anthony D Harris[SUP] 7 [/SUP], Jean Clement[SUP] 7 [/SUP], Joseph M Dybas[SUP] 8 [/SUP], Nukhet Aykin-Burns[SUP] 9 [/SUP], Joseph W Guarnieri[SUP] 8 [/SUP], Larry N Singh[SUP] 8 [/SUP], Peter Grabham[SUP] 10 [/SUP], Stephen B Baylin[SUP] 11 [/SUP], Aliza Yousey[SUP] 12 [/SUP], Andrea N Pearson[SUP] 13 [/SUP], Peter M Corry[SUP] 4 [/SUP], Amanda Saravia-Butler[SUP] 14 [/SUP], Thomas R Aunins[SUP] 15 [/SUP], Sadhana Sharma[SUP] 16 [/SUP], Prashant Nagpal[SUP] 17 [/SUP], Cem Meydan[SUP] 18 [/SUP], Jonathan Foox[SUP] 18 [/SUP], Christopher Mozsary[SUP] 18 [/SUP], Bianca Cerqueira[SUP] 19 [/SUP], Viktorija Zaksas[SUP] 20 [/SUP], Urminder Singh[SUP] 21 [/SUP], Eve Syrkin Wurtele[SUP] 21 [/SUP], Sylvain V Costes[SUP] 22 [/SUP], Gustavo Gastão Davanzo[SUP] 23 [/SUP], Diego Galeano[SUP] 24 [/SUP], Alberto Paccanaro[SUP] 25 [/SUP], Suzanne L Meinig[SUP] 26 [/SUP], Robert S Hagan[SUP] 26 [/SUP], Natalie M Bowman[SUP] 26 [/SUP], UNC COVID-19 Pathobiology Consortium[SUP] 26 [/SUP]; Matthew C Wolfgang[SUP] 26 [/SUP], Selin Altinok[SUP] 26 [/SUP], Nicolae Sapoval[SUP] 27 [/SUP], Todd J Treangen[SUP] 27 [/SUP], Pedro M Moraes-Vieira[SUP] 28 [/SUP], Charles Vanderburg[SUP] 29 [/SUP], Douglas C Wallace[SUP] 3 [/SUP], Jonathan C Schisler[SUP] 30 [/SUP], Christopher E Mason[SUP] 31 [/SUP], Anushree Chatterjee[SUP] 32 [/SUP], Robert Meller[SUP] 12 [/SUP], Afshin Beheshti[SUP] 33 [/SUP]
Collaborators, Affiliations
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; antiviral therapeutic; biomarker; miR-2392; miRNA; microRNA; nanoligomers.
. 2021 Sep 30;109839.
doi: 10.1016/j.celrep.2021.109839. Online ahead of print.
Role of miR-2392 in driving SARS-CoV-2 infection
J Tyson McDonald[SUP] 1 [/SUP], Francisco J Enguita[SUP] 2 [/SUP], Deanne Taylor[SUP] 3 [/SUP], Robert J Griffin[SUP] 4 [/SUP], Waldemar Priebe[SUP] 5 [/SUP], Mark R Emmett[SUP] 6 [/SUP], Mohammad M Sajadi[SUP] 7 [/SUP], Anthony D Harris[SUP] 7 [/SUP], Jean Clement[SUP] 7 [/SUP], Joseph M Dybas[SUP] 8 [/SUP], Nukhet Aykin-Burns[SUP] 9 [/SUP], Joseph W Guarnieri[SUP] 8 [/SUP], Larry N Singh[SUP] 8 [/SUP], Peter Grabham[SUP] 10 [/SUP], Stephen B Baylin[SUP] 11 [/SUP], Aliza Yousey[SUP] 12 [/SUP], Andrea N Pearson[SUP] 13 [/SUP], Peter M Corry[SUP] 4 [/SUP], Amanda Saravia-Butler[SUP] 14 [/SUP], Thomas R Aunins[SUP] 15 [/SUP], Sadhana Sharma[SUP] 16 [/SUP], Prashant Nagpal[SUP] 17 [/SUP], Cem Meydan[SUP] 18 [/SUP], Jonathan Foox[SUP] 18 [/SUP], Christopher Mozsary[SUP] 18 [/SUP], Bianca Cerqueira[SUP] 19 [/SUP], Viktorija Zaksas[SUP] 20 [/SUP], Urminder Singh[SUP] 21 [/SUP], Eve Syrkin Wurtele[SUP] 21 [/SUP], Sylvain V Costes[SUP] 22 [/SUP], Gustavo Gastão Davanzo[SUP] 23 [/SUP], Diego Galeano[SUP] 24 [/SUP], Alberto Paccanaro[SUP] 25 [/SUP], Suzanne L Meinig[SUP] 26 [/SUP], Robert S Hagan[SUP] 26 [/SUP], Natalie M Bowman[SUP] 26 [/SUP], UNC COVID-19 Pathobiology Consortium[SUP] 26 [/SUP]; Matthew C Wolfgang[SUP] 26 [/SUP], Selin Altinok[SUP] 26 [/SUP], Nicolae Sapoval[SUP] 27 [/SUP], Todd J Treangen[SUP] 27 [/SUP], Pedro M Moraes-Vieira[SUP] 28 [/SUP], Charles Vanderburg[SUP] 29 [/SUP], Douglas C Wallace[SUP] 3 [/SUP], Jonathan C Schisler[SUP] 30 [/SUP], Christopher E Mason[SUP] 31 [/SUP], Anushree Chatterjee[SUP] 32 [/SUP], Robert Meller[SUP] 12 [/SUP], Afshin Beheshti[SUP] 33 [/SUP]
Collaborators, Affiliations
- PMID: 34624208
- PMCID: PMC8481092
- DOI: 10.1016/j.celrep.2021.109839
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; antiviral therapeutic; biomarker; miR-2392; miRNA; microRNA; nanoligomers.