Role of miR-2392 in driving SARS-CoV-2 infection, 2021, McDonald et al.

[SNT Gatchaman]

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

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.

Link | PDF (Cell Reports)

 

[SNT Gatchaman]

A potential avenue for an alternative antiviral agent is to target specific microRNAs (miRNAs) associated with SARS-CoV-2 infection and subsequent manifestation of COVID-19. miRNAs are non-coding RNAs involved with the regulation of post-transcriptional gene expression, and they can affect entire pathways related to viruses and diseases

miRNAs are predicted to regulate more than half of the human transcriptome

circulating miRNAs are highly stable and have the potential to be used for minimally invasive detection, as biomarkers, and as therapeutic targets

we report on a miRNA, miR-2392, that may directly regulate and drive a COVID-19 response. This miRNA is predicted from COVID-19 RNA sequencing (RNA-seq) patient data that resulted in multiple miRNAs being suppressed/inhibited (miR-10, miR-10a-5p, miR-1-3p, miR-34a-5, miR-30c-5p, miR-29b-3p, miR-155-5p, and miR-124-3p) and one miRNA being upregulated (miR-2392).

we hypothesize miR-2392 to be a key miRNA involved with COVID-19 progression. Specifically, miR-2392 drives downstream suppression of mitochondria activity while increasing inflammation, glycolysis, and hypoxia.

Intriguingly, one miR-2392-predicted consequence was decreased antibody levels in the blood; this might account for the reported loss of the antibodies over time

One therapeutic insight deduced from miR-2392 interactions is the importance of the mitochondrial OXPHOS and glycolytic pathways in COVID-19

In a study of tongue squamous cell carcinoma, miR-2392 enters the mitochondrion [...] The downregulated mtDNA genes are the complex IV (cytochrome c oxidase) genes MT-CO1 and MT-CO2, the complex III (the bc 1 complex) gene (MT-CYB), and the complex I genes (MT-ND2, MT-ND4, and MT-ND5).

mitochondrial inhibition by miR-2392 appears to be the only physiological function that is common across all tissues in infected individuals, suggesting mitochondrial modulation is a central feature of SARS-CoV-2 pathophysiology.

The inhibition of mitochondrial genes by miR-2392 would impair OXPHOS, which would have the most adverse effects on the high mitochondrial energetic tissues (brain, heart, and kidney), the tissues central to the most severe COVID-19 cases.

Inhibition of mitochondrial OXPHOS genes would increase mitochondrial reactive oxygen species (mROS) production and induce glycolysis to compensate for the energy deficit

 

[FMMM1]

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.

So it seems like a potential new antiviral i.e. specific to covid*? A family member is clinically vulnerable [to covid] - so research into/availability of existing antivirals, is welcome. I can't see any evidence linking this to long covid or ME/CFS?
It does though illustrate that identifying disease mechanism can lead to the identification of a potential treatment option --- indeed developing the drug seems relatively straightforward --- there are lots of similar drugs?

*"miRNA-based antiviral therapeutic that targets miR-2392 --- may potentially inhibit a COVID-19 disease state in humans"