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Published on: May 5, 2014
Programmed -1 Ribosomal Frameshifting in coronaviruses: A therapeutic target
Jamie A Kelly1, Michael T Woodside2, Jonathan D Dinman1
1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
Abstract:
Human population growth, climate change, and globalization are accelerating the emergence of novel pathogenic viruses. In the past two decades alone, three such members of the coronavirus family have posed serious threats, spurring intense efforts to understand their biology as a way to identify targetable vulnerabilities. Coronaviruses use a programmed -1 ribosomal frameshift (-1 PRF) mechanism to direct synthesis of their replicase proteins. This is a critical switch in their replication program that can be therapeutically targeted. Here, we discuss how nearly half a century of research into -1 PRF have provided insight into the virological importance of -1 PRF, the molecular mechanisms that drive it, and approaches that can be used to manipulate it towards therapeutic outcomes with particular emphasis on SARS-CoV-2.
Insights
Emerging viruses like coronaviruses utilize a programmed -1 ribosomal frameshift (-1 PRF) for replication. Understanding this mechanism offers therapeutic targets against viral diseases, including SARS-CoV-2.
Area of Science:
- Virology
- Molecular Biology
- Emerging Infectious Diseases
Background:
- Global changes like climate change and globalization accelerate the emergence of novel pathogenic viruses.
- The coronavirus family, including SARS-CoV-2, poses significant threats due to rapid viral emergence.
- Understanding viral replication mechanisms is crucial for identifying therapeutic vulnerabilities.
Purpose of the Study:
- To review the virological significance of programmed -1 ribosomal frameshift (-1 PRF) in coronaviruses.
- To elucidate the molecular mechanisms underlying -1 PRF.
- To explore therapeutic strategies targeting -1 PRF in viral infections, with a focus on SARS-CoV-2.
Main Methods:
- Literature review of nearly 50 years of research on -1 PRF.
- Analysis of molecular mechanisms driving -1 PRF in viral replication.
- Discussion of therapeutic approaches to manipulate -1 PRF.
Main Results:
- Programmed -1 PRF is a critical mechanism for coronavirus replicase protein synthesis.
- Decades of research have illuminated the intricacies of -1 PRF.
- -1 PRF presents a druggable target for antiviral therapies.
Conclusions:
- Targeting the programmed -1 PRF mechanism offers a promising strategy for developing novel antiviral therapeutics.
- Further research into -1 PRF can yield effective treatments against emerging viral threats like SARS-CoV-2.
- The study highlights the importance of fundamental research in understanding and combating viral diseases.
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