From holding the door open to passing on a link to an exciting epigenetics paper – small gestures can make an enormous difference to anyone’s day! Now, an exciting new study suggests that the expression of a microRNA has a macro impact during SARS-CoV-2 infection and could represent an important target for the treatment of COVID-19 patients.
Specifically, researchers led by Afshin Beheshti (NASA Ames Research Center, lead researcher of the COVID-19 International Research Team) identified an overexpressed circulating microRNA in COVID-19 patients. Stable, circulating miRNAs can be used as disease-related biomarkers and therapeutic targets; therefore, the identification of this overexpressed microRNA (miR-2392) may represent a significant opportunity for the early diagnosis of SARS-CoV-2 infection and, possibly, the treatment of severe cases of COVID-19. Can a microRNA make a macro difference in the battle against COVID-19?
They say that good things come in small packages, so let’s hear all the macro details from this microRNA study by McDonald and colleagues:
- Initial analysis of RNA sequencing data from bronchial alveolar lavage fluid of COVID-19 patient highlights dysregulated miRNA expression, with seven microRNAs underexpressed and only miR-2392 overexpressed
- miR-2392 targets provide evidence for adverse health outcomes induced by the microRNA-mediated increase in inflammation and immunosuppression and a reduction in mitochondrial activity (pathways associated with SARS-CoV-2 infection)
- Overexpression of miR-2392 in human cells in vitro mimics a COVID-19 phenotype
- miR-2392 displays conservation in species affected by SARS-CoV-2 (dogs, cats, and ferrets) but not species unaffected by SARS-CoV-2 (mice and rats) and has multiple predicted binding sites within the SARS-CoV-2 genome
- The confirmation of specifically elevated miR-2392 levels in the blood and urine of COVID-19 patients by droplet digital PCR supports the development of minimally invasive methods to detect SARS-CoV-2 infection
- As miR-2392 levels increase as a function of SARS-CoV-2 load (with higher miR-2392 levels correlating with more severe disease), this microRNA has biomarker potential
- A miRNA-based antiviral therapeutic that targets miR-2392 (generated using the Nanoligomer platform) reduces SARS-CoV-2 viability in a Syrian hamster infection model
- Treatment of SARS-CoV-2-infected human lung cells in vitro with an anti-miR-2392 nanoligomer also prompts a drastic improvement in cell viability with no apparent toxicity
This exciting exploration of microRNA expression has uncovered some macro findings – the direct involvement of miR-2392 in SARS-CoV-2 infection and the identification of a possible antiviral therapeutic that inhibits COVID-19 development. The authors now hope to expand their research by exploring the expression and specificity of miR-2392 in multiple SARS-CoV-2-affected tissues in detail and further developing the nanoligomer therapeutic approach.
For more on how a microRNA can make a macro difference in the battle against COVID-19, head over to Cell Reports, September 2021.