miRNAs, from Evolutionary Junk to Possible Prognostic Markers and Therapeutic Targets in COVID-19

Abstract

The COVID-19 pandemic has been a public health issue around the world in the last few years. Currently, there is no specific antiviral treatment to fight the disease. Thus, it is essential to highlight possible prognostic predictors that could identify patients with a high risk of developing complications. Within this framework, miRNA biomolecules play a vital role in the genetic regulation of various genes, principally, those related to the pathophysiology of the disease. Here, we review the interaction of host and viral microRNAs with molecular and cellular elements that could potentiate the main pulmonary, cardiac, renal, circulatory, and neuronal complications in COVID-19 patients. miR-26a, miR-29b, miR-21, miR-372, and miR-2392, among others, have been associated with exacerbation of the inflammatory process, increasing the risk of a cytokine storm. In addition, increased expression of miR-15b, -199a, and -491 are related to the prognosis of the disease, and miR-192 and miR-323a were identified as clinical predictors of mortality in patients admitted to the intensive care unit. Finally, we address miR-29, miR-122, miR-155, and miR-200, among others, as possible therapeutic targets. However, more studies are required to confirm these findings.

MiRNA-SARS-CoV-2 dialogue and prospective anti-COVID-19 therapies

“…Viral miRNAs encoded by the SARS-CoV-2 genome guard their replication machinery and escape the host's immunity by targeting various host genes, finally attenuating it. Identification of viral miRNA could be accomplished by two main approaches, i.e., in silico analysis and sequencing of small cloned RNA [39] . Recent studies have predicted 3377 human target genes denoting it to be a unique target for 170 SARS-CoV-2 encoded matured miRNAs [40] .…”

“…In-silico study of SARS-CoV-2 encoding miRNA targets the Ca2+ signaling pathway, which acts as a key activator that subsequently affects other signaling pathways branching it. A variety of prediction tools are used to compare the resemblance of small noncoding miRNA of the host to viral miRNAs to identify an efficient target to effectively build a human-friendly therapeutic vaccine [39] . One of the computational works of Tie Ying Yu et al has identified three miRNA precursor sequences with the help of BLAST analysis of novel SARS-CoV-2 and then functionally annotated mature and precursor sequences [53] .…”

“…Liu et al conducted a computational project aiming to check the role of SARS CoV-2 encoded miRNAs in the lung tissues. Their findings suggested that viral miRNAs were associated with amplifying chemokine signaling pathways by inducing proinflammatory cytokines, mainly CXC chemokine ligand 16 (CXCL16) and arrestin beta [39] . These cytokines were predicted to be the binding targets of MR147-5p.…”

“…Despite being a cost- and time-efficient method, this theoretical foundation needs experimental validation. For this, numerous techniques are used to validate in-silico results, including microarray profiling, RNA sequencing, miRNA profiling, RT-PCR, Northern, Western, and ELISA blotting as well as immunocytochemistry [39] ( Fig. 3 ).…”

COVID-19 therapies: do we see substantial progress?

“…An important aspect of virus–host relation during SARS-CoV-2 infection and COVID-19 course is the role of miRNAs. This issue has been a subject of recent reviews [ 132 , 133 ]. One of the first known major modes of action of the virus on the host cell is sequestering of the host miRNAs [ 134 ].…”