G-Quadruplex Targeting in the Fight against Viruses: An Update

Abstract

G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in the regulation of key cellular processes, such as transcription and replication. Since their discovery, G4s have been mainly investigated for their role in cancer and as targets in anticancer therapy. More recently, exploration of the presence and role of G4s in viral genomes has led to the discovery of G4-regulated key viral pathways. In this context, employment of selective G4 ligands has helped to understand the complexity of G4-mediated mechanisms in the viral life cycle, and highlighted the possibility to target viral G4s as an emerging antiviral approach. Research in this field is growing at a fast pace, providing increasing evidence of the antiviral activity of old and new G4 ligands. This review aims to provide a punctual update on the literature on G4 ligands exploited in virology. Different classes of G4 binders are described, with emphasis on possible antiviral applications in emerging diseases, such as the current COVID-19 pandemic. Strengths and weaknesses of G4 targeting in viruses are discussed.

Biomolecules under Pressure: Phase Diagrams, Volume Changes, and High Pressure Spectroscopic Techniques

“…Naturally, not only the human genome contains GQ-forming sequences; several viral genomes were analyzed, and the potential targets of the antiviral therapy were reviewed by Ruggiero [ 147 , 148 ]. The genome of the SARS-CoV-2 virus has also been analyzed from this point of view [ 149 ], and some of the predicted viral GQs were experimentally found [ 148 , 150 ].…”

“…Naturally, not only the human genome contains GQ-forming sequences; several viral genomes were analyzed, and the potential targets of the antiviral therapy were reviewed by Ruggiero [ 147 , 148 ]. The genome of the SARS-CoV-2 virus has also been analyzed from this point of view [ 149 ], and some of the predicted viral GQs were experimentally found [ 148 , 150 ]. In my previous papers I analyzed three GQ-forming sequences of the Hepatitis B virus [ 65 , 151 ], and genomic analysis suggested the possible GQ formation of these sequences [ 152 , 153 ].…”

Imaging of Hepatitis B Virus Nucleic Acids: Current Advances and Challenges

“…Another potential target is the G4 structural motif, which has been recently identified in the pre-core promotor region of cccDNA through pulldown assays to the G4-binder DHX36 [ 120 ]. G4 structures, which form in GC-rich regions of RNA and DNA, have been identified in a variety of nucleic acids including untranslated regions of mRNAs, human telomeres, and genomes of viruses belonging to most Baltimore classes [ 121 , 122 ].…”

Never Cared for What They Do: High Structural Stability of Guanine-Quadruplexes in the Presence of Strand-Break Damage

“…For this reason, they are also of major interest in the context of the current pandemic caused by the infectious pathogen SARS-CoV-2, whose genome has been shown to contain G4-compatible regions [ 4 , 5 , 6 , 7 , 8 ]. Interesting and recent reviews on the antiviral possibilities offered by G4 can be found in literature [ 9 , 10 , 11 ]. G4s are also involved in some neurological diseases, such as alpha-thalassemia or X-linked intellectual disability syndrome, in which they are positively or negatively involved in a cascade of gene expression regulation [ 12 , 13 , 14 ].…”