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Targeting SARS-CoV-2 programmed -1 ribosomal frameshifting: structural dynamics and RNA-directed antiviral strategies
1Department of Microbiology, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India.
Antimicrobial Agents and Chemotherapy
|August 3, 2026
Summary
Programmed -1 ribosomal frameshifting (-1 PRF) is a viral mechanism regulated by RNA pseudoknots. Targeting these dynamic RNA structures offers a promising strategy for developing novel antivirals against viruses like SARS-CoV-2.
Area of Science:
- Molecular Biology
- Virology
- Structural Biology
Background:
- Programmed -1 ribosomal frameshifting (-1 PRF) is a key translational recoding mechanism in RNA viruses.
- Coronaviruses, including SARS-CoV-2, utilize a conserved RNA pseudoknot within the frameshift stimulation element to regulate viral protein expression.
Purpose of the Study:
- To review the structural organization, mechanistic basis, and conformational dynamics of viral frameshifting pseudoknots, focusing on SARS-CoV-2.
- To discuss RNA-targeted therapeutic strategies for modulating -1 PRF and their challenges.
Main Methods:
- Cryo-electron microscopy
- Single-molecule biophysics
- Molecular dynamics simulations
- Computational modeling
Main Results:
- Identified multiple pseudoknot conformations critical for translational recoding and ribosome-RNA interactions.
- Viral RNA structures, particularly pseudoknots, exhibit conformational dynamics influencing frameshifting efficiency.
- Various RNA-targeted approaches, including small molecules and oligonucleotides, show potential for antiviral development.
Conclusions:
- Viral frameshifting pseudoknots are viable targets for antiviral therapies.
- Advancements in structural biology and computational modeling aid in understanding and targeting these elements.
- Developing next-generation antivirals requires integrated strategies targeting conserved viral RNA regulatory elements.
Keywords:
RNA-targeted therapeuticsSARS-CoV-2 RNA pseudoknotconformational dynamicsprogrammed −1 ribosomal frameshiftingMore Related Videos
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