A Transcription Regulatory Sequence in the 5? Untranslated Region of SARS-CoV-2 Is Vital for Virus Replication with an Altered Evolutionary Pattern against Human Inhibitory MicroRNAs

Our knowledge of the evolution and role untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, found at 5? ends all encoded transcripts, highlighting its importance. Here, leader sequence was compared between human pathogenic non-pathogenic coronaviruses. Then, profiling microRNAs that can inactivate key UTR regions coronaviruses carried out. A distinguished pattern found. Mining available microRNA families against sequences resulted discovery 39 with a stable thermodynamic binding energy. Notably, had lower stability microRNAs. hsa-MIR-5004-3p only able to target SARS lesser extent, also SARS-CoV-2. However, decreased remarkably SARS-COV-2. We some plant low energy Meta-analysis documented significant (p < 0.01) decline expression MIR-5004-3p after SARS-COV-2 infection trachea, lung biopsy, bronchial organoids as well lung-derived Calu-3 A549 cells. The paucity innate inhibitory bind contribute high replication infected