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Antiviral Res. 2015 Jun;118:123-31. doi: 10.1016/j.antiviral.2015.03.016. Epub 2015 Apr 3.

The Herpes Simplex Virus-1 genome contains multiple clusters of repeated G-quadruplex: Implications for the antiviral activity of a G-quadruplex ligand.

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Department of Molecular Medicine, University of Padua, via Gabelli, 63, 35121 Padua, Italy.
Department of Microbiology, Infectious Diseases and Immunology, Laval University, Quebec City, Quebec, Canada.
Department of Molecular Medicine, University of Padua, via Gabelli, 63, 35121 Padua, Italy. Electronic address:


Guanine-rich nucleic acids can fold into G-quadruplexes, secondary structures implicated in important regulatory functions at the genomic level in humans, prokaryotes and viruses. The remarkably high guanine content of the Herpes Simplex Virus-1 (HSV-1) genome prompted us to investigate both the presence of G-quadruplex forming sequences in the viral genome and the possibility to target them with G-quadruplex ligands to obtain anti-HSV-1 effects with a novel mechanism of action. Using biophysical, molecular biology and antiviral assays, we showed that the HSV-1 genome displays multiple clusters of repeated sequences that form very stable G-quadruplexes. These sequences are mainly located in the inverted repeats of the HSV-1 genome. Treatment of HSV-1 infected cells with the G-quadruplex ligand BRACO-19 induced inhibition of virus production. BRACO-19 was able to inhibit Taq polymerase processing at G-quadruplex forming sequences in the HSV-1 genome, and decreased intracellular viral DNA in infected cells. The last step targeted by BRACO-19 was viral DNA replication, while no effect on virus entry in the cells was observed. This work, presents the first evidence of extended G-quadruplex sites in key regions of the HSV-1 genome, indicates the possibility to block viral DNA replication by G-quadruplex-ligand and therefore provides a proof of concept for the use of G-quadruplex ligands as new anti-herpetic therapeutic options.


Antiviral compound; DNA conformation; DNA secondary structure; G-quadruplex; G-rich sequence; Herpes Simplex Virus 1

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