A comparative analysis of G-Quadruplexes in viral genomes

1 Faculty of Chemistry, Brno University of Technology, Purkyňova 118, Brno 61200, Czech
Republic.
2 Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, Brno,
61200, Czech Republic.
 

G-quadruplexes (G4s) are non-canonical nucleic acid structures that play a pivotal role in
regulating essential molecular processes. Their potential as targets for antiviral therapies
has garnered increasing attention. We performed a comprehensive analysis of putative G-
quadruplex-forming sequences (PQS) across all viral genomes currently available in the
NCBI database, including subviral agents. Using the G4Hunter algorithm, we screened over
11,000 viral genomes totaling approximately 350 Mbp. Our findings reveal that PQS
distribution varies significantly among viral evolutionary groups. PQS are notably enriched
in genomic regions such as repeats, replication origins, and untranslated regions (5'UTRs
and 3'UTRs). Crucially, the presence and localization of PQS correlate more strongly with
the nature of the viral infection than with the type of nucleic acid. Viruses that establish
persistent infections in Metazoan hosts show a marked enrichment of PQS, whereas those
causing acute infections are significantly depleted. These patterns suggest that G-
quadruplexes may play a regulatory role in viral replication and lifecycle control. The distinct
localization of PQS highlights their potential as molecular targets for therapeutic
intervention, offering new avenues for antiviral strategy development.

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