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Updated: Jul 27, 2025
05:23
Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
Published on: December 23, 2020
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A viral pan-end RNA element and host complex define a SARS-CoV-2 regulon.
Debjit Khan1, Fulvia Terenzi1, GuanQun Liu2
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Nature Communications
|June 9, 2023
Summary
The virus SARS-CoV-2 uses a host protein, EPRS1, to bind a specific RNA element (SPEAR) on its genetic material, boosting viral replication. Targeting this interaction significantly reduces viral load, offering a potential pan-sarbecoviral therapy.
Area of Science:
- Virology
- Molecular Biology
- RNA Biology
Background:
- SARS-CoV-2 produces subgenomic RNAs (sgRNAs) with identical termini, crucial for gene expression regulation.
- The roles of these sgRNA termini and host-viral interactions in gene expression remain incompletely understood.
Purpose of the Study:
- To elucidate the mechanism by which host factors regulate SARS-CoV-2 sgRNA expression.
- To identify novel therapeutic targets for controlling SARS-CoV-2 and related viruses.
Main Methods:
- Identification of a specific RNA element (SPEAR) in viral 3'-ends.
- Investigating the binding of glutamyl-prolyl-tRNA synthetase (EPRS1) to the SPEAR element.
- Assessing the impact of SPEAR-EPRS1 interaction on viral RNA translation and frameshifting.
- Evaluating a therapeutic strategy targeting the SPEAR element.
Main Results:
- Discovered the SPEAR element in SARS-CoV-2 3'-ends, which binds EPRS1 upon induction by host agents or viral spike protein.
- Demonstrated that translation of ORF10 is essential for SPEAR-mediated induction of sgRNA expression.
- Showed that the SPEAR element enhances viral programmed ribosomal frameshifting.
- A strategy targeting SPEAR significantly reduced SARS-CoV-2 viral titers in experimental models.
Conclusions:
- SARS-CoV-2 hijacks host protein EPRS1 via the SPEAR element to enhance viral RNA translation and replication.
- The virus establishes a post-transcriptional regulon by co-opting host protein functions.
- Targeting the SPEAR-EPRS1 interaction presents a promising pan-sarbecoviral therapeutic strategy.
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