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Zika virus RNA is the single-stranded, positive-sense genomic material of the Zika virus (ZIKV), a mosquito-borne flavivirus that poses a significant threat to global public health (1, 8). The genome is approximately 10.8 kilobases in length and contains a single open reading frame flanked by highly structured 5' and 3' untranslated regions (UTRs) that are essential for viral replication and translation (3, 12, 13). These UTRs form complex secondary structures, such as Stem-Loop A (SLA), which serve as promoters for the viral polymerase and are critical for the viral life cycle (6, 17). As a therapeutic target, ZIKV RNA is approached through the development of antisense oligonucleotides, siRNAs, and small molecules designed to disrupt these essential RNA-protein or RNA-RNA interactions (2, 6, 7). By targeting the RNA directly, researchers aim to block viral translation and replication, providing a path to treat acute infections and prevent severe neurological outcomes such as microcephaly in neonates and Guillain-Barré syndrome in adults (14, 15, 16). Additionally, the production of subgenomic flavivirus RNA (sfRNA) from the 3' UTR plays a key role in antagonizing the host immune response, making it a focal point for antiviral intervention (13, 20).
Therapeutic agents target Zika virus RNA through sequence-specific hybridization to induce RNase H-mediated degradation of the viral genome or to activate the RNA-induced silencing complex (RISC) for targeted cleavage. Other strategies include the use of steric-blocking oligonucleotides that prevent ribosomal assembly and translation, or small molecules that bind to highly conserved secondary and tertiary structures, such as Stem-Loop A (SLA) in the 5' untranslated region (UTR), to inhibit the recruitment of the viral RNA-dependent RNA polymerase (NS5) and disrupt the replication complex.
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