New Insights on the Mobility of Viral and Host Non-Coding RNAs Reveal Extracellular Vesicles as Intriguing Candidate Antiviral Targets

Abstract

Intercellular communication occurring by cell-to-cell contacts and via secreted messengers trafficked through extracellular vehicles is critical for regulating biological functions of multicellular organisms. Recent research has revealed that non-coding RNAs can be found in extracellular vesicles consistent with a functional importance of these molecular vehicles in virus propagation and suggesting that these essential membrane-bound bodies can be highjacked by viruses to promote disease pathogenesis. Newly emerging evidence that coronaviruses generate non-coding RNAs and use extracellular vesicles to facilitate viral pathogenicity may have important implications for the development of effective strategies to combat COVID-19, a disease caused by infection with the novel coronavirus, SARS-CoV-2. This article provides a short overview of our current understanding of the interactions between non-coding RNAs and extracellular vesicles and highlights recent research which supports these interactions as potential therapeutic targets in the development of novel antiviral therapies.

Long Noncoding RNAs as Emerging Regulators of COVID-19

“…The latest research shows that the amino acid sequences of the SARS-CoV-2 and SARS-CoV RNA-binding domains (RBDs) are highly similar to the predicted protein structures, suggesting that SARS-CoV-2 invades host cells via ACE2 receptor ( 19 , 20 ). A recent study found that the S protein of SARS-CoV-2 strongly interacts with human ACE2 expressed by alveolar epithelial cells and can increase vascular permeability ( 23 ). In addition, the binding affinity of SARS-CoV-2 envelope spikes for the cellular ACE2 receptor is 10-20-fold higher than that of the corresponding structures of SARS-CoV, which may account for the high infectivity of the SARS-CoV-2 in humans ( 24 ).…”

Coronavirus infection: An immunologists' perspective

“…In silico and bioinformatics assessments revealed several host binding microRNA (miRNA). [56][57][58][59][60][61][62][63] Several host miRNA (15b-5p, 15a-5p, 197-5p, 548c-5p, 548d-5p, 409-3p, 30b-5p and 505-3p) may be involved blocking viral replication. 56,57 Also, viral miRNA is shared with cells miRNA (8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p), which may modulate cell response facilitating SARS-CoV-2 infection.…”

“…58 Among the different virus escape mechanisms, inhibition of host miRNA maturation, viral miRNA control of the cellular process and metabolic pathways, and viral miRNA sponges are crucial for viral escape. [56][57][58][59][60][61] IFN pathway is inhibited or downregulated, and TGF-β signalling, involved in cell suppression, is enhanced. 49,53,54 The IFN pathway inhibition affects viral RNA recognition by Toll receptors and RIG.…”

“…In silico and bioinformatics assessments revealed several host binding microRNA (miRNA) 56‐63 . Several host miRNA (15b‐5p, 15a‐5p, 197‐5p, 548c‐5p, 548d‐5p, 409‐3p, 30b‐5p and 505‐3p) may be involved blocking viral replication 56,57 .…”

“…Also, viral miRNA is shared with cells miRNA (8066, 5197, 3611, 3934‐3p, 1307‐3p, 3691‐3p, 1468‐5p), which may modulate cell response facilitating SARS‐CoV‐2 infection 58 . Among the different virus escape mechanisms, inhibition of host miRNA maturation, viral miRNA control of the cellular process and metabolic pathways, and viral miRNA sponges are crucial for viral escape 56‐61 . IFN pathway is inhibited or downregulated, and TGF‐β signalling, involved in cell suppression, is enhanced 49,53,54 .…”