Quindoline-derivatives display potent G-quadruplex-mediated antiviral activity against herpes simplex virus 1

Ilaria Frasson, Paola Soldà, Matteo Nadai, Martina Tassinari, Matteo Scalabrin, Vijay Gokhale, Laurence H. Hurley, Sara N. Richter

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


G-quadruplexes (G4s) are non-canonical nucleic acid structures that regulate key biological processes, from transcription to genome replication both in humans and viruses. The herpes simplex virus-1 (HSV-1) genome is prone to form G4s that, along with proteins, regulate its viral cycle. General G4 ligands have been shown to hamper the viral cycle, pointing to viral G4s as original antiviral targets. Because cellular G4s are also normally present in infected cells, the quest for improved anti-HSV-1 G4 ligands is still open. Here, we evaluated a series of new quindoline-derivatives which showed high binding to and stabilization of the viral G4s. They displayed nanomolar-range anti-HSV-1 activity paralleled by negligible cytotoxicity in human cells, thus proving remarkable selectivity. The best-in-class compound inhibited the viral life cycle at the early times post infection up to the step of viral genome replication. In infected human cells, it reduced expression of ICP4, the main viral transcription factor, by stabilizing the G4s embedded in ICP4 promoter. Quindoline-derivatives thus emerge as a new class of G4 ligands with potent dual anti HSV-1 activity.

Original languageEnglish (US)
Article number105432
JournalAntiviral Research
StatePublished - Dec 2022


  • Antiviral activity
  • G-quadruplex
  • HSV-1
  • ICP4
  • Quindoline derivatives

ASJC Scopus subject areas

  • Pharmacology
  • Virology


Dive into the research topics of 'Quindoline-derivatives display potent G-quadruplex-mediated antiviral activity against herpes simplex virus 1'. Together they form a unique fingerprint.

Cite this