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In Search of the Most Significant Potential G-Quadruplexes in SARS-CoV-2 RNA: Genomic Analysis.

Margarita Zarudnaya1, Ivan Voiteshenko1,2, Vasyl Hurmah1

  • 1Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150, Akademika Zabolotnoho Str., 03143 Kyiv, Ukraine.

Viruses
|February 27, 2026
PubMed
Summary

G-quadruplexes (G4s) in SARS-CoV-2 RNA are potential antiviral targets. Analysis reveals conserved G4 structures, with some influencing viral replication and protein folding, and EKM showing promise as an antiviral compound.

Keywords:
G-quadruplexesRNA secondary structure predictionSARS-CoV-2 genomedockingmolecular dynamics simulationmutational analysis

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Area of Science:

  • Virology
  • Structural Biology
  • Computational Chemistry

Background:

  • G-quadruplexes (G4s) are increasingly recognized as potential antiviral targets.
  • The SARS-CoV-2 genome contains numerous G-rich regions with putative G-quadruplex-forming sequences (PQSs).

Purpose of the Study:

  • To conduct a systematic genomic and structural analysis of SARS-CoV-2 PQSs.
  • To investigate the potential roles of G4s in viral replication, protein folding, and frameshifting.
  • To identify potential G4-targeting antiviral compounds.

Main Methods:

  • Genomic and structural analysis of SARS-CoV-2 PQSs.
  • Mutational analysis of RNA structural elements containing PQSs.
  • Molecular docking and molecular dynamics simulations to assess compound binding to G4s.

Main Results:

  • Most SARS-CoV-2 PQSs are highly conserved, with few showing G4-disrupting mutations.
  • Specific G4s may play roles in cap-independent translation, co-translational protein folding, and -1 frameshifting.
  • The compound EKM demonstrated specific binding to G4 3467, indicating potential as an antiviral agent.

Conclusions:

  • SARS-CoV-2 G4s represent conserved structural elements with significant functional implications for the viral lifecycle.
  • Targeting these G4 structures, particularly with compounds like EKM, offers a promising strategy for developing novel antiviral therapies.