Targeting G-quadruplexes to achieve antiviral activity

With the emergence of new viruses in the human population and the fast mutation rates of existing viruses, new antiviral targets and compounds are needed. Most existing antiviral drugs are active against proteins of a handful of viruses. Most of these proteins in the end affect viral nucleic acid processing, but direct nucleic acid targeting is less represented due to the difficulty of selectively acting at the nucleic acid of interest. Recently, nucleic acids have been shown to fold in structures alternative to the classic double helix and Watson and Crick base-pairing. Among these non-canonical structures, G-quadruplexes (G4s) have attracted interest because of their key bio-logical roles that are being discovered. Molecules able to selectively target G4s have been developed and since G4s have been investigated as targets in several human pathologies, including viral infections. Here, after briefly introducing viruses, G4s and the G4-binding molecules with antiviral properties, we comment on the mecha-nisms at the base of the antiviral activity reported for G4-binding molecules. Understanding how G4-ligands act in infected cells will possibly help designing and developing next-generation antiviral drugs.

Automated summary

With the emergence and fast mutation rates of new viruses, there is a need for new antiviral targets and compounds. Most existing antiviral drugs target only a few specific viruses by affecting viral nucleic acid processing. However, selectively targeting nucleic acids of interest is challenging. Recently, G-quadruplexes (G4s), which are alternative structures to the classic double helix, have attracted attention due to their important biological roles. Molecules that selectively target G4s have been developed and investigated as potential antiviral drugs for various human pathologies, including viral infections.