@article{972180bf1d114cd3a0028ef752fa19bb,
title = "Role of miR-2392 in driving SARS-CoV-2 infection",
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",
author = "{UNC COVID-19 Pathobiology Consortium} and McDonald, {J. Tyson} and Enguita, {Francisco J.} and Deanne Taylor and Griffin, {Robert J.} and Waldemar Priebe and Emmett, {Mark R.} and Sajadi, {Mohammad M.} and Harris, {Anthony D.} and Jean Clement and Dybas, {Joseph M.} and Nukhet Aykin-Burns and Guarnieri, {Joseph W.} and Singh, {Larry N.} and Peter Grabham and Baylin, {Stephen B.} and Aliza Yousey and Pearson, {Andrea N.} and Corry, {Peter M.} and Amanda Saravia-Butler and Aunins, {Thomas R.} and Sadhana Sharma and Prashant Nagpal and Cem Meydan and Jonathan Foox and Christopher Mozsary and Bianca Cerqueira and Viktorija Zaksas and Urminder Singh and Wurtele, {Eve Syrkin} and Costes, {Sylvain V.} and Davanzo, {Gustavo Gast{\~a}o} and Diego Galeano and Alberto Paccanaro and Meinig, {Suzanne L.} and Hagan, {Robert S.} and Bowman, {Natalie M.} and Wallet, {Shannon M.} and Robert Maile and Wolfgang, {Matthew C.} and Mock, {Jason R.} and Torres-Castillo, {Jose L.} and Love, {Miriya K.} and Will Lovell and Colleen Rice and Olivia Mitchem and Dominique Burgess and Jessica Suggs and Jordan Jacobs and Selin Altinok and Nicolae Sapoval",
note = "Funding Information: This work was supported by supplemental funds for COVID-19 research from Translational Research Institute of Space Health through NASA Cooperative Agreement NNX16AO69A (T-0404 to A.B. and T-0406 to A.C.) and further funding from KBR, Inc. (to A.B.). This work used resources, services, and support provided via the COVID-19 HPC Consortium (https://covid19-hpc-consortium.org/), specifically by the NASA High-End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center (to A.B.); DOD W81XWH-21-1-0128 (to D.C.W.); NIGMS P20 GM1009005 (to N.A.-B.); Individual National Research Service award F32-AI147587 (to J.M.D.); NIH/NHBLI K08 HL143271 and NIH/NHLBI R03 HL155249 (to R.S.H.); NIH/NCI U54 CA260543 (supporting R.S.H. N.M.B. and M.C.W.); and NSF 1956233 (to R.M.). A.P. was supported by Biotechnology and Biological Sciences Research Council (https://bbsrc.ukri.org/) grants BB/K004131/1, BB/F00964X/1, and BB/M025047/1; Consejo Nacional de Ciencia y Tecnolog{\'i}a Paraguay (CONACyT) (https://www.conacyt.gov.py/) grants 14-INV-088 and PINV15-315; and National Science Foundation Advances in Bio Informatics (https://www.nsf.gov/) grant 1660648. E.S.W. was supported by NSF IOS 1546858. D.G. and A.P. were supported by CONACYT grant PINV20-337 and the Funda{\c c}{\~a}o Getulio Vargas. N.M.B. was supported by the National Center for Advancing Translational Sciences (NCATS) and NIH UL1TR002489, 2KR1272005, and 550KR242003. P.M.M.-V. was supported by FAPESP grants 20/04579-7 and 16/18031-8; Fundo de Apoio ao Ensino, Pesquisa e Extens{\~a}o (FAEPEX); Unicamp grant 2274/20; and Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior-Brazil (CAPES) (finance code 001). Thanks to Dr. Richard Bowen for his assistance with the hamster studies and Dr. Matthew Frieman for his assistance with the in vitro A549 SARS-CoV-2 studies. The graphical abstract was created with BioRender.com and partially adapted from “Bevacizumab: Potential Repurposed Drug Candidate for COVID-19” retrieved from https://app.biorender.com/biorender-templates. Conceptualization: A.B.; methodology: A.B.; formal analysis: A.B. R.M. C.V. D.T. F.J.E. C. Meydan, C. Mozsary, J.C.S. J.T.M. J.M.D. D.G. U.S. E.S.W. A.S.-B. J.F. V.Z. N.S. and T.J.T.; investigation: A.B. C.V. R.M. C.E.M. A.C. P.N. S.L.M. A.Y. A.N.P. T.R.A. P.M.M.-V. and G.G.D.; sample collection: M.M.S. M.C.W. R.S.H. N.M.B. UNC COVID-19 Pathobiology Consortium, A.D.H. J.C. P.M.M.-V. and G.G.D.; resources: A.B. R.M. C.E.M. A.C. and M.C.W.; writing – original draft: A.B. and J.T.M.; writing – review & editing: A.B. J.T.M. F.J.E. R.J.G. W.P. M.M.S. J.M.D. J.W.G. D.C.W. S.S. S.B.B. V.Z. E.S.W. S.V.C. N.A.-B. A.P. D.G. P.M.C. M.R.E. J.C.S. S.A. A.C. R.M. N.S. T.J.T. B.C. L.N.S. P.G. M.C.W. and P.M.M.-V.; visualization: A.B. J.C.S. F.J.E. D.G. N.S. and V.Z.; supervision: A.B.; funding acquisition: A.B. A.C. P.N. S.V.C. and A.B. have a provisional patent based on the antiviral discovery and design. A.C. P.N. and S.S. are part of the company (Sachi Bioworks Inc.) that has filed a patent on the Nanoligomer technology. Funding Information: This work was supported by supplemental funds for COVID-19 research from Translational Research Institute of Space Health through NASA Cooperative Agreement NNX16AO69A ( T-0404 to A.B. and T-0406 to A.C.) and further funding from KBR, Inc. (to A.B.). This work used resources, services, and support provided via the COVID-19 HPC Consortium ( https://covid19-hpc-consortium.org/ ), specifically by the NASA High-End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center (to A.B.); DOD W81XWH-21-1-0128 (to D.C.W.); NIGMS P20 GM1009005 (to N.A.-B.); Individual National Research Service award F32-AI147587 (to J.M.D.); NIH/NHBLI K08 HL143271 and NIH/NHLBI R03 HL155249 (to R.S.H.); NIH/NCI U54 CA260543 (supporting R.S.H., N.M.B., and M.C.W.); and NSF 1956233 (to R.M.). A.P. was supported by Biotechnology and Biological Sciences Research Council ( https://bbsrc.ukri.org/ ) grants BB/K004131/1 , BB/F00964X/1 , and BB/M025047/1 ; Consejo Nacional de Ciencia y Tecnolog{\'i}a Paraguay (CONACyT) ( https://www.conacyt.gov.py/ ) grants 14-INV-088 and PINV15-315 ; and National Science Foundation Advances in Bio Informatics ( https://www.nsf.gov/ ) grant 1660648 . E.S.W. was supported by NSF IOS 1546858 . D.G. and A.P. were supported by CONACYT grant PINV20-337 and the Funda{\c c}{\~a}o Getulio Vargas . N.M.B. was supported by the National Center for Advancing Translational Sciences (NCATS) and NIH UL1TR002489 , 2KR1272005 , and 550KR242003 . P.M.M.-V. was supported by FAPESP grants 20/04579-7 and 16/18031-8 ; Fundo de Apoio ao Ensino, Pesquisa e Extens{\~a}o (FAEPEX); Unicamp grant 2274/20 ; and Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior-Brazil (CAPES) (finance code 001 ). Thanks to Dr. Richard Bowen for his assistance with the hamster studies and Dr. Matthew Frieman for his assistance with the in vitro A549 SARS-CoV-2 studies. The graphical abstract was created with BioRender.com and partially adapted from “Bevacizumab: Potential Repurposed Drug Candidate for COVID-19” retrieved from https://app.biorender.com/biorender-templates . Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = oct,
day = "19",
doi = "10.1016/j.celrep.2021.109839",
language = "English (US)",
volume = "37",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}