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.
【저자키워드】 COVID-19, Drug repurposing, Biomarker, microRNA, variant discovery, nanoparticle vaccine, SARS-CoV-2 replication, microRNA vaccine, 【초록키워드】 Meta-analysis, Evolution, SARS-CoV-2, Coronaviruses, coronavirus, knowledge, SARS-COV-2 infection, Infection, lung, binding energy, Replication, Region, stability, leader sequence, pathogenicity, UTR, expression, MicroRNAs, Calu-3, binding, A549, Profiling, Trachea, untranslated region, lung biopsy, sequence, human cells, transcripts, A549 cells, pathogenic, inhibitory, bronchial organoids, carried, contribute, highlighting, thermodynamic, bronchial organoid, 【제목키워드】 SARS-CoV-2, Human, Region, pattern, untranslated region, Altered, Vital,