Conserved 3' UTR of Severe Acute Respiratory Syndrome Coronavirus 2: Potential Therapeutic Targets.

Abstract

Our previous paper showed that microRNAs (miRNAs) present within human placental or mesenchymal stem cell-derived extracellular vesicles (EVs) directly interacted with the RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), inhibiting viral replication. In this paper, we analyzed whether these miRNAs could exert antiviral activity against other variants of SARS-CoV-2. We downloaded compete SARS-CoV-2 genome data submitted to the National Center for Biotechnology Information for each SARS-CoV-2 variant, aligned the data to the reference SARS-CoV-2 genome sequence, and then confirmed the presence of 3′ untranslated region (UTR) mutations. We identified one type of 3′ UTR mutation in the Alpha variant, four in the Beta variant, four in the Gamma variant, three in the Delta variant, and none in the Omicron variant. Our findings indicate that 3′ UTR mutations rarely occur as persistent mutations. Interestingly, we further confirmed that this phenomenon could suppress virus replication in the same manner as the previously discovered interaction of placental-EV-derived miRNA with 3′ UTRs of SARS-CoV-2. Because the 3′ UTR of the SARS-CoV-2 RNA genome has almost no mutations, it is expected to be an effective therapeutic target regardless of future variants. Thus, a therapeutic strategy targeting the 3′ UTR of SARS-CoV-2 is likely to be extremely valuable, and such an approach is also expected to be applied to all RNA-based virus therapeutics.