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Related Experiment Video

Updated: Jun 16, 2025

Production of A SARS-CoV-2 Virus like Particle System to Investigate Viral Life Cycles In Vitro
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Stem loop binding protein promotes SARS-CoV-2 replication via -1 programmed ribosomal frameshifting.

Tanxiu Chen1,2,3, Ruimin Zhu1, Tingfu Du2

  • 1State Key Laboratory of Respiratory Health and Multimorbidity, National Center of Technology Innovation for Animal Model, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Institute of Laboratory Animal Science, CAMS & PUMC, Beijing, China.

Signal Transduction and Targeted Therapy
|June 13, 2025
PubMed
Summary
This summary is machine-generated.

Stem Loop Binding Protein (SLBP) promotes SARS-CoV-2 frameshifting, a key viral process. This discovery identifies SLBP as a potential therapeutic target for COVID-19 treatment.

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Area of Science:

  • Virology
  • Molecular Biology
  • Host-Pathogen Interactions

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) relies on -1 programmed ribosomal frameshifting (-1 PRF) for polyprotein synthesis.
  • Host factors regulating SARS-CoV-2 -1 PRF remain largely unidentified, limiting therapeutic strategies.

Purpose of the Study:

  • To identify host proteins that interact with SARS-CoV-2 -1 PRF RNA.
  • To investigate the role of identified host proteins in viral replication and frameshifting.
  • To explore potential therapeutic targets for COVID-19.

Main Methods:

  • RNA pull-down assays coupled with mass spectrometry to identify interacting host proteins.
  • Deep learning prediction (PrismNet) for RNA-protein binding probability.
  • Electrophoretic Mobility Shift Assays (EMSAs) and RNA pull-down assays to confirm direct binding.
  • Small fluorescent microscopy in situ hybridization (smFISH) for colocalization studies.
  • In vitro translation systems to assess frameshifting efficiency.

Main Results:

  • Five host proteins, including Stem Loop Binding Protein (SLBP), were identified interacting with -1 PRF RNA.
  • SLBP directly binds to the SARS-CoV-2 -1 PRF RNA, particularly the stem loop 3 region.
  • SLBP overexpression enhances -1 PRF and promotes viral replication.
  • SLBP influences the binding of other host factors (FUBP3, RPS3A, RPL10A) to the -1 PRF RNA region.

Conclusions:

  • Stem Loop Binding Protein (SLBP) is a novel host factor that promotes SARS-CoV-2 -1 PRF.
  • SLBP's interaction with viral RNA is crucial for efficient viral replication.
  • SLBP represents a potential druggable target for developing novel COVID-19 therapeutics.