G-quadruplexes contribute to the regulation of key molecular processes. Their utilization for antiviral therapy is an emerging field of contemporary research. Here we present comprehensive analyses of the presence and localization of putative G-quadruplex forming sequences (PQS) in all viral genomes currently available in the NCBI database (including subviral agents). The G4Hunter algorithm was applied to a pool of 11,000 accessible viral genomes representing 350 Mbp in total. PQS frequencies differ across evolutionary groups of viruses, and are enriched in repeats, replication origins, 5'UTRs and 3'UTRs. Importantly, PQS presence and localization is connected to viral lifecycles and corresponds to the type of viral infection rather than to nucleic acid type; while viruses routinely causing persistent infections in Metazoa hosts are enriched for PQS, viruses causing acute infections are significantly depleted for PQS. The unique localization of PQS identifies the importance of G-quadruplex-based regulation of viral replication and life cycle, providing a tool for potential therapeutic targeting.

Brno University of Technology Faculty of Mechanical Engineering Technická 2896 2 616 69 Brno Czech Republic

Brno University of Technology Faculty of Mechanical Engineering Technická 2896 2 616 69 Brno Czech Republic; Department of Informatics Mendel University in Brno Zemědělská 1 Brno 613 00 Czech Republic

Department of Biology and Ecology Institute of Environmental Technologies Faculty of Science University of Ostrava Ostrava 710 00 Czech Republic

Institute of Biophysics of the Czech Academy of Sciences Královopolská 135 Brno 612 65 Czech Republic

Institute of Biophysics of the Czech Academy of Sciences Královopolská 135 Brno 612 65 Czech Republic; Department of Experimental Biology Faculty of Science Masaryk University Kamenice 5 62500 Brno Czech Republic

Institute of Biophysics of the Czech Academy of Sciences Královopolská 135 Brno 612 65 Czech Republic; Laboratoire d'Optique et Biosciences Ecole Polytechnique CNRS INSERM Institut Polytechnique de Paris 91128 Palaiseau France

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