Decoding the Structural Complexity of Viral RNAs with SHAPE to Guide Antiviral Therapeutics

Area of Science:

• Virology
• Molecular Biology
• Structural Biology

Background:

• Viral RNA genomes possess regulatory elements beyond protein-coding sequences.
• These elements control viral life cycle stages like translation, replication, and host immune evasion.
• RNA secondary structures and RNA-RNA interactions are crucial for viral function.

Purpose of the Study:

• To review experimental strategies for profiling viral RNA architecture.
• To discuss functional RNA structures identified in diverse viral families.
• To examine structure-guided approaches for antiviral intervention.

Main Methods:

• Focus on Selective 2′-Hydroxyl Acylation analyzed by primer extension (SHAPE) and its high-throughput derivatives.
• Integration of complementary chemical probing approaches.
• Genome-wide structural profiling at single nucleotide resolution.

Main Results:

• Viral genomes are highly structured, containing functional elements in both untranslated and coding regions.
• Identified key structures include internal ribosome entry sites (IRES), cyclization elements, XRN1-resistant elements, and frameshifting elements.
• Structure-based analyses reveal numerous functional RNA elements across viral families.

Conclusions:

• Viral RNA structure is a critical determinant of virus biology.
• Structure-guided analysis opens new avenues for antiviral therapies.
• Antiviral strategies include antisense oligonucleotides, small molecules, and RNA-degrading chimeras targeting viral RNA structures.