Potential Use of Noncoding RNAs and Innovative Therapeutic Strategies to Target the 5’UTR of SARS-CoV-2

Figure 1.. Alignment of 5'UTR regions of three coronaviruses. Alignment of (A) the first part (100 nucleotides) of the 5’UTR of three coronavirus isolates that show the similarity of the leader sequence (colored in green and blue) and the IGS depicted in brown. The position 56, considered crucial for viral transcription is represented in red. Blue and black lines indicate the genomic regions where siRNAs reported in the literature have been designed; (B) the alignment of complete 5’UTR region showing the similitude of the leader sequences and the high conservation of the transcription-regulatory sequence in SARS-CoV and SARS-CoV-2. IGS: Intergenic sequence; SARS-CoV: Severe acute respiratory syndrome coronavirus; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; TRS: Transcription-regulatory sequence.

Figure 2.. Secondary structures of the first 95–100 nucleotides of common coronavirus such as infectious bronchitis virus, MERS, severe acute respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2 showing the structural similarity of the first stem loop structure.

Figure 3.. Secondary structures of the 5’UTR region of severe acute respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2 that emphasize the structural similarity of these two coronaviruses.

Figure 4.. Aligned 5’UTR of severe acute respiratory syndrome coronavirus and severe acute respiratory syndrome coronaviruses 2 and the identification of miRNA binding sites. miRNAs targeting one site are depicted in blue, whereas in red if they target two sites (such as miR-3150-3p and miR-602).

Figure 5.. Antisense LNA GapmeRs. Schematic representation of (A) the functioning of GapmeRs oligonucleotides made by a DNA oligonucleotide 5’- and 3’-linked to two LNA terminals that is able to activate the degradation of mRNA by RNase H; (B) GapmeRs indicated with numbers have been designed starting from the 5’UTR sequence. LNA: Locked nucleic acid.