One microRNA has the potential to target whole viral mRNAs in a given human coronavirus

MicroRNAs (miRNAs) can repress viral replication by targeting viral messenger RNA (mRNA), which makes them potential antiviral agents. The antiviral effects of miRNAs on infectious viruses have been explored extensively; however, recent studies mainly considered the action modes of miRNAs, neglecting another key factor, the molecular biology of viruses, which may be particularly important in the study of miRNA actions against a given virus. In this paper, the action modes of miRNAs and the molecular biology of viruses are jointly considered for the first time and based on the reported roles of miRNAs on viruses and human coronaviruses (HCoVs) molecular biology, the general and specific interaction modes of miRNAs-HCoVs are systematically reviewed. It was found that HCoVs transcriptome is a nested set of subgenomic mRNAs, sharing the same 5' leader, 3' untranslated region (UTR) and open reading frame (ORF). For a given HCoV, one certain miRNA with a target site in the 5' leader or 3' UTR has the potential to target all viral mRNAs, indicating tremendous antiviral effects against HCoVs. However, for the shared ORFs, some parts are untranslatable attributed to the translation pattern of HCoVs mRNA, and it is unknown whether the base pairing between the untranslated ORFs and miRNAs plays a regulatory effect on the local mRNAs where the untranslated ORFs are located; therefore, the regulatory effects of miRNAs with targets within the shared ORFs are complicated and need to be confirmed. Collectively, miRNAs may bepromising antiviral agents against HCoVs due to their intrinsically nested set of mRNAs, and some gaps are waiting to be filled. In this review, insight is provided into the exploration of miRNAs that can interrupt HCoVs infection.