Journal
CELLS
Volume 10, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/cells10020319
Keywords
COVID-19; biomarker; drug repurposing; microRNA; SARS-CoV-2 replication; microRNA vaccine; nanoparticle vaccine; variant discovery
Categories
Funding
- National Collaborative Research Infrastructure Strategy (NCRIS)
- Australian Government
- Government of Western Australia
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This study reveals a distinct pattern of evolution in the leader sequence of SARS-CoV-2 and identifies several microRNAs with stable binding energy against coronaviruses, including hsa-MIR-5004-3p which targets both SARS and SARS-CoV-2 with reduced stability in the latter. Lack of innate human inhibitory microRNAs binding to the leader sequence of SARS-CoV-2 may contribute to its high replication in infected human cells.
Our knowledge of the evolution and the role of untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, is found at the 5 ' ends of all encoded SARS-CoV-2 transcripts, highlighting its importance. Here, evolution of leader sequence was compared between human pathogenic and non-pathogenic coronaviruses. Then, profiling of microRNAs that can inactivate the key UTR regions of coronaviruses was carried out. A distinguished pattern of evolution in leader sequence of SARS-CoV-2 was found. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with a stable thermodynamic binding energy. Notably, SARS-CoV-2 had a lower binding stability against microRNAs. hsa-MIR-5004-3p was the only human microRNA able to target the leader sequence of SARS and to a lesser extent, also SARS-CoV-2. However, its binding stability decreased remarkably in SARS-COV-2. We found some plant microRNAs with low and stable binding energy against SARS-COV-2. Meta-analysis documented a significant (p < 0.01) decline in the expression of MIR-5004-3p after SARS-COV-2 infection in trachea, lung biopsy, and bronchial organoids as well as lung-derived Calu-3 and A549 cells. The paucity of the innate human inhibitory microRNAs to bind to leader sequence of SARS-CoV-2 can contribute to its high replication in infected human cells.
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