Schematic overview of the SARS-CoV-2 genome and target sequences of the siRNAs in the 5′-UTR. (A) Schematic overview of the SARS-CoV-2 genome, the subgenomic RNAs and the virion structure. The coronavirus virion consists of the structural spike protein (S), envelope protein (E), membrane protein (M) and nucleoprotein (N). The single-stranded RNA genome with positive polarity is encapsulated by N, while S-trimers protrude from the host-derived virus envelope and enable binding to new host cells. In addition to the genomic RNA, nine subgenomic RNAs are synthesized during replication, all of which share the same 5′- and 3′-ends. The orange box represents the mutual 5′-end, the leader sequence. (B) Target sequences of the siRNAs in the 5′-UTR of SARS-CoV-2. The leader sequence (light orange) and the transcription regulatory sequence (TRS, dark orange) can be found at the 5′-end of the genomic and subgenomic RNAs. Nucleotides without an asterisk differ from the SARS-CoV-1 5′-UTR sequence.