G-Quadruplexes in Neurobiology and Virology: Functional Roles and Potential Therapeutic Approaches

[Image: see text] A G-quadruplex (G4) is a four-stranded nucleic acid secondary structure maintained by Hoogsteen hydrogen bonds established between four guanines. Experimental studies and bioinformatics predictions support the hypothesis that these structures are involved in different cellular functions associated with both DNA and RNA processes. An increasing number of diseases have been shown to be associated with abnormal G4 regulation. Here, we describe the existence of G4 and then discuss G4-related pathogenic mechanisms in neurodegenerative diseases and the viral life cycle. Furthermore, we focus on the role of G4s in the design of antiviral therapy and neuropharmacology, including G4 ligands, G4-based aptamers, G4-related proteins, and CRISPR-based sequence editing, along with a discussion of limitations and insights into the prospects of this unusual nucleic acid secondary structure in therapeutics. Finally, we highlight progress and challenges in this field and the potential G4-related research fields.