ArticleVirus research2026
Paradoxical G-quadruplex distribution in coronavirus genomes reveals functional constraints and antiviral therapeutic opportunities.
Article in Virus research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
We computationally characterized G-quadruplex (G4) distributions across 31 coronavirus genomes to identify conserved structural features as potential antiviral therapeutic targets. Through an integrated approach combining consensus G4 detection, dinucleotide-preserving null models, and pooled Poisson rate ratios, we identified a paradoxical G4 distribution pattern: genome-wide depletion (mean fold change = 0.56) coupled with strong regional enrichment in Spike (S) protein (incidence rate ratio [IRR] = 17.9; 95% CI: 11.7-27.6) and Nucleocapsid (N) protein (IRR = 15.2; 95% CI: 8.7-26.6), while untranslated regions (UTRs) showed complete G4 absence. Thermodynamic stability assessment identified 38 stable G4 candidates (ΔG < -5 kcal/mol), with 52.6% concentrated in Nucleocapsid protein regions, suggesting candidates for structure-based antiviral drug development awaiting experimental confirmation. This paradoxical distribution pattern-genome-wide depletion coupled with strong regional enrichment in functionally critical proteins (Spike and Nucleocapsid)-provides a mechanistic framework for developing betacoronavirus-targeted therapeutics based on conserved G4 structures.
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